Abstract
Psychostimulants, including cocaine, have two opposing effects on dopamine (DA) neurons: a DA-mediated inhibition and a non-DA-mediated excitation. The latter, expressed as an increase in both firing rate and a slow oscillation (SO) in firing pattern, has been shown to require forebrain inputs to DA neurons and activation of adrenergic α1 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 α1-mediated excitatory effect, consistently inhibited all three measures of DA cell activity. Blockade of α1 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, α1 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.
Footnotes
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This work was supported in part by National Institute on Drug Abuse DA12944 (to W.-X.S.) and a National Alliance for Research on Schizophrenia and Depression Distinguished Investigator Award (to B.S.B.).
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doi:10.1124/jpet.105.094045.
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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.
- Received August 9, 2005.
- Accepted December 2, 2005.
- The American Society for Pharmacology and Experimental Therapeutics
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