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NEUROPHARMACOLOGY
1 Receptors and Comparison with L-Dopa and Apomorphine
Neuropsychopharmacological Research Unit, Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
Received August 9, 2005; accepted December 2, 2005.
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1 receptors. However, since the effect was observed when the DA-mediated inhibition was blocked by a D2 antagonist, it is uncertain whether the underlying mechanism also plays a role in cocaine's effects in normal animals where D2-like receptors are not blocked. This study showed that under such conditions, cocaine decreased firing rate and bursting without significantly inhibiting the SO in DA neurons recorded in the ventral tegmental area. Different from cocaine, L-dopa and apomorphine, two nonpsychostimulant DA agonists known to lack the 1-mediated excitatory effect, consistently inhibited all three measures of DA cell activity. Blockade of 1 receptors by prazosin did not enhance cocaine's ability to inhibit firing rate and bursting, but it did enable cocaine to inhibit the SO. These results suggest that in control rats where D2-like receptors are not blocked, 1 receptors play an important role in cocaine's effect on the SO but not in its effect on firing rate and bursting of DA neurons. The maintained SO after cocaine injection may reflect continued modulation of DA neurons by forebrain inputs, regulate the pattern of DA release, and provide a temporal structure for selection of synaptic inputs to DA neurons.
; Bunney and Aghajanian, 1976, 1978; Einhorn et al., 1988; Lacey et al., 1990; Shi et al., 2000a). After these DA-mediated feedback mechanisms are blocked by a D2 antagonist, psychostimulants excite DA neurons instead of producing no effect (Shi et al., 2000b, 2004). The excitation, expressed as an increase in both firing rate and a slow oscillation (SO) in firing pattern (Shi et al., 2004; Shi, 2005), has been shown to persist when both D1- and D2-like receptors are blocked. The effect is mimicked by the norepinephrine (NE) uptake blocker nisoxetine, but not by the indirect DA agonist L-dopa, and is eliminated by adrenergic 1 antagonists such as prazosin, suggesting that the effect is non-DA-mediated, involving activation of 1 receptors (Shi et al., 2000b, 2004). Part of the effect may be due to activation of 1 receptors on DA neurons (Grenhoff et al., 1995; Paladini et al., 2001). However, since it is largely blocked when forebrain inputs to DA neurons are interrupted (Shi et al., 2000b, 2004), the effect may also involve activation of 1 receptors in forebrain areas. Consistent with this possibility, local infusion of the 1 antagonist prazosin into the prefrontal cortex mimics the effect of systemically administered prazosin, blocking both functional DA release and locomotor activation induced by D-amphetamine (Darracq et al., 1998).
The above-described excitatory effect of cocaine was observed when D2-like receptors were blocked by a D2 antagonist. In this study, we asked whether 1 receptors also play a role in cocaine's effects in control animals where D2-like receptors are not blocked. Under such conditions, cocaine has been shown to inhibit DA neurons, indicating that the D2-mediated inhibitory effect is more dominant than the 1-mediated excitatory effect. The presence of the latter effect, however, may oppose the D2-mediated inhibition, resulting in a reduced inhibitory effect of cocaine on DA neurons. If this hypothesis is correct, blockade of 1 receptors should enhance the ability of cocaine to inhibit DA neurons. It is also possible, however, that the neuronal pathway responsible for the 1-mediated excitatory effect is under the control of DA receptors, and is inhibited by cocaine when D2-like receptors are not blocked, in which case blockade of 1 receptors should have no influence on cocaine's ability to inhibit DA neurons.
To test the above possibilities, two series of experiments were performed. First, rats were pretreated with prazosin to block 1 receptors to determine whether this blockade enhances cocaine's ability to inhibit DA neurons. In the second series of experiments, we compared effects of cocaine with those of L-dopa and apomorphine, two nonpsychostimulant DA agonists known to also inhibit DA cell firing but lack the 1-mediated excitatory effect (Shi et al., 2000b, 2004). As described above, the 1-mediated excitation is associated with an increase in not only firing rate but also the SO in firing pattern. We therefore predicted that in control rats, all three DA agonists decrease DA cell firing through D2-like receptors, but they produce different effects on firing pattern of DA neurons because of their different ability to activate the 1-mediated excitatory mechanism. We further predicted that prazosin-pretreatment eliminates the difference between cocaine and the two nonpsychostimulant DA agonists.
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, 2004). Briefly, glass microelectrodes were made using a Narishige electrode puller (Narishige, East Meadow, NY), filled with a 2 M NaCl solution containing 2% Pontamine Sky Blue dye and had an impedance ranging from 7 to 15 M
. A small burr hole was drilled above the VTA (2.8–3.2 mm anterior to the lambdoidal suture and 0.5–1.0 mm lateral to the midline), through which an electrode was lowered using an electric microdrive. DA cells were typically found between 6.5 to 8.5 mm below the cortical surface. They were identified by well established electrophysiological criteria (Bunney et al., 1973; Grace and Bunney, 1983; Ungless et al., 2004), which include a biphasic (positive-negative) or triphasic (positive-negative-positive) spike wave form with a duration of greater than 3.0 ms, a broad initial positive phase (>1 ms, measured from the start of action potential to the negative trough), an initial segment-somatodendritic break in the initial positive phase, a slow firing rate (<10 spikes/s), and an irregular firing pattern. DA neurons also differ from neighboring non-DA neurons by the characteristic low-pitched sound they produce on an audio monitor. One main goal of this study was to determine effects of cocaine, L-dopa, and apomorphine on firing pattern of DA neurons. For this purpose, DA neurons that had very low baseline firing rates (<2 spikes/s) were excluded from this study because they tended to be completely inhibited by these DA agonists and, thus, could not be used for further analysis of changes in firing pattern. Interspike intervals (ISIs) were collected on line via an interface (Lab-PC+, National Instrument, Austin, TX) to a Windows-based PC computer using in-house software written in LabView for Windows. Throughout the experiment, body temperature was maintained at 36–38°C with a heating pad. Only one cell was studied in each rat. Drugs. Drugs used in this study were cocaine hydrochloride, L-dopa methyl ester hydrochloride, apomorphine hydrochloride hemihydrate, and prazosin hydrochloride. All were purchased from Sigma-RBI (St. Louis, MO) and injected intravenously through a lateral tail vein. In experiments involving multiple injections, each injection was separated by approximately 3 to 5 min. All doses given refer to the salts. Prazosin was dissolved in 25 to 30% poly(ethylene glycol) (PEG, average mol. wt. 200) at 2.5 mg/ml. Before injection, the solution was diluted with distilled water so that the final volume of injection was 0.1 ml. Depending on the weight of the animal, the final concentration of PEG ranged from 14 to 20%. All other drugs were dissolved in distilled water.
Data Analysis. All data analyses were performed in Microsoft Excel using in-house Visual Basic programs. The onset of a burst was identified by two consecutive spikes with an ISI less than 80 ms, and the termination of a burst was defined as an ISI greater than 160 ms (Grace and Bunney, 1984). The level of bursting was measured by the number of spikes occurred in bursts. The variability of firing was evaluated by the variation coefficient (CV) of ISIs, which was calculated by dividing the standard deviation of ISIs by the mean ISI. Firing rate, bursting, and CV were determined every 10 s. Firing periodicity was analyzed using methods similar to those described previously (Shi et al., 2004; Shi, 2005). Briefly, rate histograms and autocorrelograms (autocovariance with a binwidth of 50 ms over 2048 bins) were constructed based on 2-min recordings obtained under different conditions. Following tapering using the Hanning-Tukey window function (15 windows with 50% overlap) and removal of the linear trend, the Fast Fourier Transform was performed to yield spectra with a resolution of 0.078 Hz. Spectra obtained from rate histograms and autocorrelograms were qualitatively identical. For simplicity, this study reports only the results from the Fast Fourier Transform of autocorrelograms. To help visualize slow changes, rate histograms were smoothed using methods described previously (Shi et al., 2004; Shi, 2005). All spectral results, however, were obtained based on analysis of unsmoothed data.
Effects of drugs and their differences between experimental groups were evaluated by comparing recordings (2-min duration) obtained under different conditions using ANOVA or ANCOVA followed by a post hoc Tukey test. The covariate was either baseline value or the value immediately before the injection of the drug of interest. Spectral data were log-transformed before being subjected to statistical comparison. All numerical results were expressed as mean ± S.E.M.
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1 receptors enhances cocaine's ability to inhibit DA neurons, rats were pretreated with prazosin (0.5 mg/kg i.v., n = 18). Effects of cocaine (1 mg/kg given in single or two doses i.v.) were then determined and compared with those observed in control (n = 26) and vehicle-treated rats (PEG, n = 9). The results showed that 1 blockade did not significantly alter cocaine's inhibitory effect on firing rate and bursting, but it did enable cocaine to inhibit the variability of firing (CV).
Figure 1, A and B, shows recordings from two DA neurons, one from a control rat and one from a prazosin-pretreated rat. Figure 1C summarizes results from all cells tested. On average, the firing rate of DA neurons was decreased by cocaine from 50.8 ± 3.2 to 30.2 ± 3.5, 60.7 ± 4.6 to 27.3 ± 3.9, and 55.0 ± 2.3 to 29.6 ± 2.4 spikes/10 s, respectively, in the control (n = 26, p < 0.001, post hoc Tukey test following ANCOVA), vehicle-treated (n = 9, p < 0.001), and prazosin-treated groups (n = 18, p < 0.001). The degree of inhibition was not significantly different between groups (F2,49 = 1.87, p = 0.17, ANCOVA), suggesting that blockade of 1 receptors does not enhance cocaine's ability to inhibit DA neurons. Baseline firing rate was not significant different between groups (F2,50 = 2.00, p = 0.15, ANOVA), and was unaffected by vehicle (p = 0.85, post hoc Tukey test following ANCOVA) or prazosin treatment (p = 1.00).
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The level of bursting (spikes fired in bursts) was also decreased by cocaine in all three groups (control: from 17.4 ± 3.6 to 6.5 ± 2.6 spikes in bursts/10 s, n = 26, p < 0.001; vehicle-treated: from 25.7 ± 6.4 to 1.2 ± 1.6, n = 9, p < 0.001; prazosin-treated: 14.6 ± 4.6 to 0.5 ± 0.2, n = 18, p < 0.001). Again, the effect observed in the prazosin-treated group was not significantly different from that seen the control (p = 0.09) or vehicle-treated group (p = 0.74). Baseline bursting was not significantly different between groups (F2,50 = 1.59, p = 0.21) and was unaffected by vehicle (p = 0.74) and prazosin (p = 0.98).
CV was unchanged (<5% change, n = 4) or increased (n = 13) by cocaine in the majority of cells tested in the control group. In the remaining cells (n = 9), CV was decreased. On average, CV was unchanged (from 63.2 ± 5.7 to 68.3 ± 4.5%, n = 26, p = 0.09). A nonsignificant effect of cocaine was also observed in vehicle-treated rats (from 70.3 ± 9.2 to 62.6 ± 7.6, n = 9, p = 0.41). In prazosin-pretreated rats, however, cocaine consistently decreased CV (from 64.6 ± 6.9 to 41.0 ± 4.0, n = 18, p < 0.001). ANCOVA followed by post hoc tests confirmed that cocaine's effect in prazosin-treated rats was significantly different from that in control (p < 0.001) or vehicle-treated rats (p < 0.01). Baseline CV was similar between groups (F2,50 = 0.55, p = 0.58) and was unaltered by vehicle (p = 0.79) or prazosin (p = 0.66).
Effects of Cocaine on the Oscillatory Properties of DA Neurons. In rats with D2-like receptors blocked, cocaine has been shown to increase the SO in DA neurons and prazosin blocks the effect (Shi et al., 2004). This study found that in control rats, cocaine produced either no effect or an increase in the SO in the majority of cells tested. When 1 receptors were blocked by prazosin, cocaine consistently suppressed the SO. Figure 2 shows data from three different DA neurons. Two were recorded from control rats and one from a prazosin-pretreated rat. Of the two cells recorded in control rats, one showed a significant SO before cocaine injection (Fig. 2B) and one did not (Fig. 2A, see also Shi, 2005). In both cells, cocaine increased the SO. In the cell recorded in a prazosin-pretreated rat, cocaine inhibited not only firing rate and bursting but also the SO (Fig. 2D).
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Effects of L-Dopa and Apomorphine. Results above suggest that in control rats, 1 receptor activation prevents cocaine from significantly decreasing CV and the SO, predicting that a DA agonist without 1 agonist properties would inhibit these measures. To test this possibility, effects of L-dopa (100 mg/kg i.v., n = 10) and apomorphine (10 µg/kg i.v., n = 11) were examined. Both agonists have been previously shown to inhibit DA cell firing but lack the 1-mediated excitatory effect (Shi et al., 2000b, 2004). In all cells tested, both were found to inhibit firing rate and bursting as well as CV and the SO.
Figure 4, A and B, shows responses of two typical DA neurons tested with L-dopa and apomorphine, respectively. Figure 5 summarizes results from all cells tested. For comparison, results with cocaine (1 mg/kg i.v.) are also included in Fig. 5. Both L-dopa and apomorphine inhibited firing rate (L-dopa: from 56.7 ± 3.0 to 43.3 ± 3.3 spikes/10 s, p < 0.001; apomorphine: from 59.5 ± 2.5 to 39.3 ± 2.4 spikes/10 s, p < 0.001) and bursting (L-dopa: from 20.3 ± 6.2 to 3.2 ± 1.9 total spikes in bursts/10 s, p < 0.001; apomorphine: from 13.4 ± 5.8 to 2.5 ± 1.9, p < 0.001). At the doses used, the degree of inhibition induced by the two drugs was not significantly different from that induced by cocaine (firing rate: F2,43 = 1.26, p = 0.29; bursting: F2,43 = 2.25, p = 0.12). Different from cocaine, however, L-dopa and apomorphine consistently decreased CV (L-dopa: from 64.7 ± 9.2 to 47.6 ± 8.1%, p < 0.001; apomorphine: from 53.3 ± 11.2 to 35.1 ± 9.6%, p < 0.001). ANCOVA followed by post hoc tests confirmed the difference between the effect of cocaine and that of L-dopa (p < 0.001) and apomorphine (p < 0.001). Also different from cocaine, L-dopa and apomorphine decreased the SO in all cells tested (L-dopa: from 0.20 ± 0.19 to 0.04 ± 0.04%, F1,17 = 61.32, p < 0.001; apomorphine: from 0.05 ± 0.04 to 0.01 ± 0.01%, F1,19 = 25.71, p < 0.001). ANCOVA followed by post hoc tests confirmed the difference between the effect of cocaine and that of L-dopa (p < 0.05) or apomorphine (p < 0.001).
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1 receptors when D2-like receptors are blocked. This study shows that in control rats where D2-like receptors are not blocked, 1 receptors also play a role in cocaine's effects on DA neurons. In these animals, cocaine inhibits firing rate and bursting without significantly inhibiting the variability of firing (CV) and the SO. Different from cocaine, L-dopa and apomorphine inhibit all four measures of DA cell activity. Blockade of 1 receptors by prazosin enables cocaine to inhibit CV and the SO, but has no influence on cocaine's ability to inhibit firing rate and bursting. These results suggest that in normal animals where D2-like receptors are not blocked, 1 receptors play an important role in cocaine's effect on firing pattern, but not on firing rate of DA neurons.
Multiple Effects of Cocaine on DA Neurons. Psychostimulants including cocaine had long been thought to have only one effect on the firing activity of DA neurons: a D2-mediated feedback inhibition (Bunney and Aghajanian, 1976, 1978; Einhorn et al., 1988; Lacey et al., 1990). We have recently shown that these drugs can also act through 1 receptors to excite DA neurons when the D2-mediated inhibition is blocked (see Introduction). This finding is consistent with the fact that psychostimulants also bind to NE transporters to increase NE release and/or to block NE reuptake, and with previous studies showing that stimulation of the locus coeruleus excites DA neurons in a prazosin-sensitive manner (Collingridge et al., 1979; Grenhoff et al., 1993). Previous studies using brain slices have shown that 1 receptor activation directly depolarizes a subset of DA neurons (Grenhoff et al., 1995) and indirectly increases DA cell excitability by blocking the metabotropic glutamate receptor-mediated inhibitory effect (Paladini et al., 2001). Our results suggest that the excitatory effect of cocaine observed in vivo also depends on forebrain inputs to DA neurons. Using spectral analysis, we have further shown that the effect is associated with an increase in not only firing rate and bursting, but also CV and the SO. These effects are mimicked by all psychostimulants tested, but not by L-dopa and apomorphine, and are blocked by the 1 antagonist prazosin (Shi et al., 2000b, 2004).
In this study, we showed that the same parameters of DA cell activity were suppressed by cocaine in rats with 1 receptors blocked by prazosin. The suppression is likely to be mediated by D2-like receptors since cocaine produces no significant effects on DA neurons when both 1 and D2-like receptors are blocked (Shi et al., 2004). Consistent with this suggestion, L-dopa and apomorphine, two DA agonists lacking 1 agonist properties, also inhibited all four measures, and the inhibition was blocked by a D2 antagonist (Shi et al., 2000b, 2004).
DA-NE Interaction in Cocaine's Effects on DA Neurons. Effects of cocaine described above were observed in the presence of either 1 or D2-like receptor blockade. In control rats where neither receptor was blocked, cocaine inhibited DA cell firing and bursting. Since blockade of 1 receptors by prazosin did not enhance cocaine's ability to inhibit the two parameters, one may conclude that the 1-mediated excitatory mechanism is not activated under such conditions and, therefore, has no contribution to cocaine's effects. However, prazosin did significantly enhance cocaine's ability to inhibit CV and the SO. These findings raise the possibility that there are two different 1 receptor-mediated mechanisms. One is involved in cocaine's effects on firing rate and bursting, and one on CV and the SO. In control rats, the former is inhibited by cocaine through D2-like receptors, whereas the latter is not inhibited or is only partially inhibited by cocaine. Consequently, prazosin enhances the ability of cocaine to inhibit CV and the SO without significantly altering cocaine's ability to inhibit firing rate and bursting.
An important factor not considered in the above discussion is that an oscillatory input, activated by cocaine through 1 receptors, may produce different responses in a DA neuron depending on the level of membrane potential. At the rest or a depolarized state, such as when cocaine is given in the presence of D2 blockade, an oscillatory input may cause a net increase in firing rate because spikes evoked by the depolarizing phase of the oscillation are greater than those inhibited by the hyperpolarizing phase of the same oscillation. Consequently, blockade of the oscillatory input by prazosin reverses the increase in both firing rate and the SO caused by the oscillatory input. In control rats, cocaine hyperpolarizes DA neurons (Lacey et al., 1990). During the hyperpolarization, the same oscillatory input may be less effective in increasing spikes during its depolarizing phase and more effective in inhibiting the firing during its hyperpolarizing phase. As a result, the oscillatory input may produce no effect or only a small increase in firing rate, in which case removal by prazosin of the oscillatory input would inhibit the SO without significantly altering firing rate. Thus, further investigations are needed to confirm whether effects of cocaine on different parameters are mediated by the same or different mechanisms.
It should be pointed out that in control rats, although the majority of DA cells showed no change or an increase in CV and the SO in responding to cocaine injection, some showed a decrease. Correlation analysis suggests that cells of the latter group tended to have higher baseline CV and SO, suggesting that the mechanism responsible for the SO may have already been activated before cocaine injection and, therefore, is less sensitive to further activation of 1 receptors. This suggestion, however, is inconsistent with the finding that prazosin produced no significant effect on baseline CV and SO (see also Shi, 2005). Thus, the cause of the differences between cells remains to be determined.
Potential Significances of 1 Receptor-Mediated Effects of Cocaine. The maintained variability of firing and SO seen after cocaine injection may reflect continued modulation of DA neurons by afferent inputs. In rats with forebrain inputs interrupted, DA neurons fired in a highly regular manner and showed no SO (Shi, 2005). DA neurons in these lesioned rats also showed no increase in the SO in response to psychostimulant injection (Shi et al., 2004). In this study, we found that L-dopa and apomorphine decreased CV and the SO, suggesting that the two nonpsychostimulant DA agonists differ from cocaine and may cause a functional disconnection of DA neurons from their afferent inputs. It may be relevant to note that prazosin, which enables cocaine to inhibit CV and the SO, decreases the psychomotor stimulant effect of both cocaine and amphetamine (e.g., Snoddy and Tessel, 1985; Berthold et al., 1992; Drouin et al., 2002; Wellman et al., 2002). In a recent study, prazosin is also shown to attenuate cocaine-induced reinstatement of drug-seeking behavior without altering lever pressing for food (Zhang and Kosten, 2005). Several groups, however, failed to demonstrate a significant effect of prazosin on cocaine-induced behaviors (Thiebot et al., 1981; Filip et al., 2001; Vanderschuren et al., 2003). The cause of the discrepancy is unclear and may be related to different experimental procedures, drug doses, and strain and species of animals used.
The maintained variability of firing and the SO may affect both the pattern of DA release from DA terminals and information processing in DA soma and dendrites. Oscillatory firing may lead to an oscillatory DA release, which may affect DA receptive neurons differently from a tonic DA release (Goto and Grace, 2005). Since cocaine blocks DA reuptake, the SO seen after cocaine injection may affect the dynamics of both intra and extrasynaptic DA levels (Floresco et al., 2003). The SO can also have a strong influence on how synaptic information is processed and transmitted by DA neurons. Fluctuations of ongoing activity, especially in the form of oscillations, have been shown to play an important role in input selection, synaptic plasticity, phase coding, and synchrony between neurons (Engel et al., 2001; Buzsaki and Draguhn, 2004). Thus, further understanding of the 1-mediated effect of cocaine may provide crucial new insights into why this drug is both highly addictive and psychotogenic.
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ABBREVIATIONS: DA, dopamine; SO, slow oscillation; NE, norepinephrine; VTA, ventral tegmental area; ISI, interspike interval; PEG, poly(ethylene glycol); CV, variation coefficient; ANOVA, analysis of variance; ANCOVA, analysis of covariance.
Address correspondence to: Dr. Wei-Xing Shi, Neuropsychopharmacological Research Unit, Yale University School of Medicine, 300 George Street, Room 8300C, New Haven, CT 06511. E-mail: wei-xing.shi{at}yale.edu
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References |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
Berthold CW 3rd, Gonzales RA, and Moerschbaecher JM (1992) Prazosin attenuates the effects of cocaine on motor activity but not on schedule-controlled behavior in the rat. Pharmacol Biochem Behav 43: 111–115.[CrossRef][Medline]
Bunney BS and Aghajanian GK (1976) D-Amphetamine-induced inhibition of central dopaminergic neurons: mediation by a striato-nigral feedback pathway. Science (Wash DC) 192: 391–393.
Bunney BS and Aghajanian GK (1978) D-Amphetamine-induced depression of central dopamine neurons: evidence for mediation by both autoreceptors and a striatonigral feedback pathway. Naunyn-Schmiedeberg's Arch Pharmacol 304: 255–261.[CrossRef][Medline]
Bunney BS, Walters JR, Roth RH, and Aghajanian GK (1973) Dopaminergic neurons: effect of antipsychotic drugs and amphetamine on single cell activity. J Pharmacol Exp Ther 185: 560–571.
Buzsaki G and Draguhn A (2004) Neuronal oscillations in cortical networks. Science (Wash DC) 304: 1926–1929.
Collingridge GL, James TA, and MacLeod NK (1979) Neurochemical and electrophysiological evidence for a projection from the locus coeruleus to the substantia nigra [proceedings]. J Physiol (Lond) 290: 44P.[Medline]
Darracq L, Blanc G, Glowinski J, and Tassin JP (1998) Importance of the noradrenaline-dopamine coupling in the locomotor activating effects of D-amphetamine. J Neurosci 18: 2729–2739.
Drouin C, Blanc G, Villegier AS, Glowinski J, and Tassin JP (2002) Critical role of alpha1-adrenergic receptors in acute and sensitized locomotor effects of D-amphetamine, cocaine and GBR 12783: influence of preexposure conditions and pharmacological characteristics. Synapse 43: 51–61.[CrossRef][Medline]
Einhorn LC, Johansen PA, and White FJ (1988) Electrophysiological effects of cocaine in the mesoaccumbens dopamine system: studies in the ventral tegmental area. J Neurosci 8: 100–112.[Abstract]
Engel AK, Fries P, and Singer W (2001) Dynamic predictions: oscillations and synchrony in top-down processing. Nat Rev Neurosci 2: 704–716.[CrossRef][Medline]
Filip M, Nowak E, and Papla I (2001) On the role of serotonin2A/2C receptors in the sensitization to cocaine. J Physiol Pharmacol 52: 471–481.[Medline]
Floresco SB, West AR, Ash B, Moore H, and Grace AA (2003) Afferent modulation of dopamine neuron firing differentially regulates tonic and phasic dopamine transmission. Nat Neurosci 6: 968–973.[CrossRef][Medline]
Goto Y and Grace AA (2005) Dopaminergic modulation of limbic and cortical drive of nucleus accumbens in goal-directed behavior. Nat Neurosci 8: 805–812.[CrossRef][Medline]
Grace AA and Bunney BS (1983) Intracellular and extracellular electrophysiology of nigral dopaminergic neurons–1. Identification and characterization. Neuroscience 10: 301–315.[CrossRef][Medline]
Grace AA and Bunney BS (1984) The control of firing pattern in nigral dopamine neurons: burst firing. J Neurosci 4: 2877–2890.[Abstract]
Grenhoff J, Nisell M, Ferre S, Aston-Jones G, and Svensson TH (1993) Noradrenergic modulation of midbrain dopamine cell firing elicited by stimulation of the locus coeruleus in the rat. J Neural Transm Gen Sect 93: 11–25.[CrossRef][Medline]
Grenhoff J, North RA, and Johnson SW (1995) Alpha 1-adrenergic effects on dopamine neurons recorded intracellularly in the rat midbrain slice. Eur J Neurosci 7: 1707–1713.[CrossRef][Medline]
Lacey MG, Mercuri NB, and North RA (1990) Actions of cocaine on rat dopaminergic neurones in vitro. Br J Pharmacol 99: 731–735.[Medline]
Paladini CA, Fiorillo CD, Morikawa H, and Williams JT (2001) Amphetamine selectively blocks inhibitory glutamate transmission in dopamine neurons. Nat Neurosci 4: 275–281.[CrossRef][Medline]
Shi WX (2005) Slow oscillatory firing: a major firing pattern of dopamine neurons in the ventral tegmental area. J Neurophysiol 94: 3516–3522.
Shi WX, Pun CL, Smith PL, and Bunney BS (2000a) Endogenous DA-mediated feedback inhibition of DA neurons: involvement of both D(1)- and D(2)-like receptors. Synapse 35: 111–119.[CrossRef][Medline]
Shi WX, Pun CL, Zhang XX, Jones MD, and Bunney BS (2000b) Dual effects of D-amphetamine on dopamine neurons mediated by dopamine and nondopamine receptors. J Neurosci 20: 3504–3511.
Shi WX, Pun CL, and Zhou Y (2004) Psychostimulants induce low-frequency oscillations in the firing activity of dopamine neurons. Neuropsychopharmacology 29: 2160–2167.[CrossRef][Medline]
Shi WX, Smith PL, Pun CL, Millet B, and Bunney BS (1997) D1–D2 interaction in feedback control of midbrain dopamine neurons. J Neurosci 17: 7988–7994.
Snoddy AM and Tessel RE (1985) Prazosin: effect on psychomotor-stimulant cues and locomotor activity in mice. Eur J Pharmacol 116: 221–228.[CrossRef][Medline]
Thiebot MH, Kloczko J, Chermat R, Puech AJ, Soubrie P, and Simon P (1981) Enhancement of cocaine-induced hyperactivity in mice by benzodiazepines: evidence for an interaction of GABAergic processes with catecholaminergic neurons? Eur J Pharmacol 76: 335–343.[CrossRef][Medline]
Ungless MA, Magill PJ, and Bolam JP (2004) Uniform inhibition of dopamine neurons in the ventral tegmental area by aversive stimuli. Science (Wash DC) 303: 2040–2042.
Vanderschuren LJ, Beemster P, and Schoffelmeer AN (2003) On the role of noradrenaline in psychostimulant-induced psychomotor activity and sensitization. Psychopharmacology (Berl) 169: 176–185.[CrossRef][Medline]
Wellman P, Ho D, Cepeda-Benito A, Bellinger L, and Nation J (2002) Cocaine-induced hypophagia and hyperlocomotion in rats are attenuated by prazosin. Eur J Pharmacol 455: 117–126.[CrossRef][Medline]
Zhang XY and Kosten TA (2005) Prazosin, an -1 adrenergic antagonist, reduces cocaine-induced reinstatement of drug-seeking. Biol Psychiatry 57: 1202–1204.[CrossRef][Medline]
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P0.5–1.5Hz) was modestly correlated with baseline P0.5–1.5Hz (left) and strongly correlated with cocaine's effect on CV (
