Lack of tolerance to nicotine-induced dopamine release in the nucleus accumbens

doi:10.1016/0014-2999(89)90798-X

European Journal of Pharmacology

Volume 168, Issue 3, 22 September 1989, Pages 363-368

https://doi.org/10.1016/0014-2999(89)90798-X Get rights and content

Abstract

The extent to which repeated administration produces tolerance to nicotine-induced increases in dopamine transmission in the nucleus accumbens was investigated in rats. In vivo microdialysis was used to sample extracellular dopamine and metabolites after a nicotine challenge (0.35 mg/kg) in (1) naive rats, (2) acutely pretreated rats (1 prior nicotine injection), and (3) chronically pretreated rats (12—15 prior daily nicotine injections, 0.35 mg/kg per injection). Nicotine increased extracellular DA and its metabolites, and these increases were not significantly altered by either acute or chronic prior exposure to the drug. The failure to find evidence of tolerance is compatible with the hypothesis that the mesolimbic dopaminergic system is a substrate for the reinforcing properties of chronically administered nicotine.

References (28)

M.D. Aceto et al.
Rapid and brief tolerance to (+)- and (−)-nicotine in unanesthetized rats
European J. Pharmacol.
(1986)
B.C. Barrass et al.
Modification of nicotine toxicity by pretreatment with different drugs
Biochem. Pharmacol.
(1969)
G. Damsma et al.
The effect of systemically applied cholinergic drugs on the striatal release of dopamine and its metabolites, as determined by automated brain dialysis in conscious rats
Neurosci. Lett.
(1988)
J.E. Henningfield et al.
Nicotine as a reinforcer in human subjects and laboratory animals
Pharmacol. Biochem. Behav.
(1983)
J.E. Hubbard et al.
Tolerance development to the arousal effects of nicotine
Pharmacol. Biochem. Behav.
(1975)
A. Imperato et al.
Nicotine preferentially stimulates dopamine release in the limbic system of freely moving rats
European J. Pharmacol.
(1986)
E.P. Lapin et al.
Dopamine-like action of nicotine: lack of tolerance and reverse tolerance
Brain Res.
(1987)
M.J. Marks et al.
Tolerance, cross-tolerance, and receptors after chronic nicotine or oxotremorine
Pharmacol. Biochem. Behav.
(1985)
B.H.C. Westerink et al.
Scope and limitations of in vivo brain dialysis: a comparison of its application to various neurotransmitter systems
Life Sci.
(1987)
P.B.S. Clarke
Nicotine and smoking: a perspective from animal studies
Psychopharmacology
(1987)

P.B.S. Clarke et al.

Evidence that mesolimbic dopaminergic activation underlies the locomotor stimulant action of nicotine in rats

J. Pharmacol. Exp. Ther.

(1988)

P.B.S. Clarke et al.

The effects of nicotine on locomotor activity in non-tolerant rats

Br. J. Pharmacol.

(1983)

P.B.S. Clarke et al.

Characterization of the locomotor stimulant action of nicotine in tolerant rats

Br. J. Pharmacol.

(1983)

B.M. Cox et al.

Nicotine self-administration in rats

Br. J. Pharmacol.

(1984)

Cited by (153)

Age-contingent influence over accumbal neurotransmission and the locomotor stimulatory response to acute and repeated administration of nicotine in Wistar rats
2015, Neuropharmacology
Citation Excerpt :
Especially, interrupted drug-exposure appears to produce an incubation effect, facilitating this process (Abdolahi et al., 2010; Pickens et al., 2011). Interestingly, locomotor sensitization appears to be established prior to nicotine-induced enhancement of dopamine release (Damsma et al., 1989; Vezina et al., 2007). This is also supported by our microdialysis experiments, which revealed no effect by treatment on nicotine-induced dopamine release in the NAc during the first days of nicotine-withdrawal.
Nicotine addiction is one of the leading contributors to the global burden of disease, and early onset smokers report a more severe addiction with lower chance of cessation than those with a late onset. Preclinical research supports an age-dependent component to the rewarding and reinforcing properties of nicotine, and the aim of this study was to define behavioral adaptations and changes in accumbal neurotransmission that arise over 15 days of intermittent nicotine treatment (0.36 mg/kg/day) in rats of three different ages (5 weeks, 10 weeks, 36 weeks old). Repeated treatment increased the locomotor stimulatory response to nicotine in all age groups, but significantly faster in the two younger groups. In addition, nicotine decreased rearing activity in a way that sustained even after repeated administration in aged rats but not in the younger age groups. Electrophysiological field potential recordings revealed a decline in input/output function in the nucleus accumbens (NAc) of animals intermittently treated with nicotine starting at 5 weeks of age, but not in older animals. In drug naïve rats, acute administration of nicotine modulated both accumbal dopamine output and excitatory transmission in a partially age-dependent manner. Fifteen days of intermittent nicotine treatment did not alter the acute effect displayed by nicotine on dopamine levels or evoked field potentials. The data presented here show that both acute and repeated nicotine administration modulates accumbal neurotransmission and behavior in an age-contingent manner and that these age-dependent differences could reflect important neurobiological underpinnings associated with the increased vulnerability for nicotine-addiction in adolescents.
A positive relationship between harm avoidance and brain nicotinic acetylcholine receptor availability
2013, Psychiatry Research - Neuroimaging
Prior research indicates that disturbance of cholinergic neurotransmission reduces anxiety, leading to the hypothesis that people with heightened cholinergic function have a greater tendency toward anxiety-like and/or harm-avoidant behavior. We sought to determine if people with elevated levels of harm avoidance (HA), a dimension of temperament from the Temperament and Character Inventory (TCI), have high α4β2⁎ nicotinic acetylcholine receptor (nAChR) availability. Healthy adults (n=105; 47 non-smokers and 58 smokers) underwent bolus-plus-continuous infusion positron emission tomography (PET) scanning using the radiotracer 2-[18F]fluoro-3-(2(S)azetidinylmethoxy) pyridine (abbreviated as 2-FA). During the uptake period of 2-FA, participants completed the TCI. The central study analysis revealed a significant association between total HA and mean nAChR availability, with higher total HA scores being linked with greater nAChR availability. In examining HA subscales, both ‘Fear of Uncertainty’ and ‘Fatigability’ were significant, based on higher levels of these characteristics being associated with greater nAChR availabilities. This study adds to a growing body of knowledge concerning the biological basis of personality and may prove useful in understanding the pathophysiology of psychiatric disorders (such as anxiety disorders) that have similar characteristics to HA. Study findings may indicate that heightened cholinergic neurotransmission is associated with increased anxiety-like traits.
Exercise as a novel treatment for drug addiction: A neurobiological and stage-dependent hypothesis
2013, Neuroscience and Biobehavioral Reviews
Citation Excerpt :
During early “non-addicted” stages, such as when drug use is initiated, dopamine signaling in the reward pathway (i.e., nucleus accumbens, NAc; ventral tegmental area, prefrontal cortex, PFC) is believed to be a primary mechanism motivating drug use (for reviews see Gardner, 2011; Kalivas and Volkow, 2005; Koob and Volkow, 2010; Pierce and Kumaresan, 2006; Willuhn et al., 2010). Drugs of abuse, including psychostimulants, alcohol, nicotine, hallucinogens, cannabinoids, and opiates increase dopamine in the NAc (Carboni et al., 1989; Chen et al., 1990; Damsma et al., 1989; Di Chiara and Imperato, 1988; Hernandez and Hoebel, 1988; Maisonneuve et al., 1991; Yoshimoto et al., 1992). Blocking/ablating this pathway can disrupt drug self-administration, particularly psychostimulant self-administration (e.g., Chang et al., 1994; Corrigall et al., 1992; Lyness et al., 1979; Singer et al., 1982; Singer and Wallace, 1984; Robledo et al., 1992; but see Lyness and Smith, 1992 for ethanol self-administration and Gerrits and Van Ree, 1996 for heroin self-administration).
Physical activity, and specifically exercise, has been suggested as a potential treatment for drug addiction. In this review, we discuss clinical and preclinical evidence for the efficacy of exercise at different phases of the addiction process. Potential neurobiological mechanisms are also discussed focusing on interactions with dopaminergic and glutamatergic signaling and chromatin remodeling in the reward pathway. While exercise generally produces an efficacious response, certain exercise conditions may be either ineffective or lead to detrimental effects depending on the level/type/timing of exercise exposure, the stage of addiction, the drug involved, and the subject population. During drug use initiation and withdrawal, its efficacy may be related to its ability to facilitate dopaminergic transmission, and once addiction develops, its efficacy may be related to its ability to normalize glutamatergic and dopaminergic signaling and reverse drug-induced changes in chromatin via epigenetic interactions with brain-derived neurotrophic factor (BDNF) in the reward pathway. We conclude with future directions, including the development of exercise-based interventions alone or as an adjunct to other strategies for treating drug addiction.
Beta2-containing nicotinic acetylcholine receptors mediate calcium/calmodulin-dependent protein kinase-II and synapsin i protein levels in the nucleus accumbens after nicotine withdrawal in mice
2013, European Journal of Pharmacology
Citation Excerpt :
Indeed, the nicotine induced increase in ventral tegmental area dopamine neuron firing rate (Grenhoff et al., 1986), and subsequent dopamine release in the nucleus accumbens is a process thought to underlie the addictive properties of nicotine (Pontieri et al., 1996). Compatible with the current studies, acute nicotine increases dopamine release in the nucleus accumbens, and tolerance does not develop to chronic-nicotine induced increases in dopamine release (Damsma et al., 1989; Nisell et al., 1997). In our withdrawal assessment, DHβE (2 mg/kg, s.c.) at a dose that precipitates significant nicotine withdrawal-induced aversion in mice (Jackson et al., 2009b), but not MLA, precipitated a significant decrease in CaMKII and synapsin I activity in the nucleus accumbens.
Nicotinic acetylcholine receptors are calcium-permeable and the initial targets for nicotine. Studies suggest that calcium-dependent mechanisms mediate some behavioral responses to nicotine; however, the post-receptor calcium-dependent mechanisms associated with chronic nicotine and nicotine withdrawal remain unclear. The proteins calcium/calmodulin-dependent protein kinase II (CaMKII) and synapsin I are essential for neurotransmitter release and were shown to be involved in drug dependence. In the current study, using pharmacological techniques, we sought to (a) complement previously published behavioral findings from our lab indicating a role for calcium-dependent signaling in nicotine dependence and (b) expand on previously published acute biochemical and pharmacological findings indicating the relevance of calcium-dependent mechanisms in acute nicotine responses by evaluating the function of CaMKII and synapsin I after chronic nicotine and withdrawal in the nucleus accumbens, a brain region implicated in drug dependence. Male mice were chronically infused with nicotine for 14 days, and treated with the β2-selective antagonist dihydro-β-erythroidine (DHβE), or the α7 antagonist, methyllycaconitine citrate (MLA) 20 min prior to dissection of the nucleus accumbens. Results show that phosphorylated and total CaMKII and synapsin I protein levels were significantly increased in the nucleus accumbens after chronic nicotine infusion, and reduced after treatment with DHβE, but not MLA. A spontaneous nicotine withdrawal assessment also revealed significant reductions in phosphorylated CaMKII and synapsin I levels 24 h after cessation of nicotine treatment. Our findings suggest that post-receptor calcium-dependent mechanisms associated with nicotine withdrawal are mediated through β2-containing nicotinic receptors.
Frontoparietal attentional network activation differs between smokers and nonsmokers during affective cognition
2013, Psychiatry Research - Neuroimaging
Smoking withdrawal-induced disruption of affect and cognition is associated with dysregulated prefrontal brain function, although little is known regarding the neural foci of smoker–nonsmoker differences during affective cognition. Thus, the current study used functional magnetic resonance imaging (fMRI) to identify smoker–nonsmoker differences in affective cognition. Thirty-four healthy volunteers (17 smokers, 17 nonsmokers) underwent fMRI during an affective Stroop task (aST). The aST includes emotional cue-reactivity trials, and response selection trials that contain either neutral or negative emotional distractors. Smokers had less activation during negative cue-reactivity trials in regions subserving emotional awareness (i.e., posterior cingulate), inhibitory control (i.e., inferior frontal gyrus) and conflict resolution (i.e., anterior cingulate); during response-selection trials with negative emotional distractors, smokers had greater activation in a frontoparietal attentional network (i.e., middle frontal and supramarginal gyri). Exploratory analyses revealed that task accuracy was positively correlated with anterior cingulate cortex and inferior frontal gyrus response on fMRI. These findings suggests that chronic nicotine use may reduce inhibitory control and conflict resolution of emotional distraction, and result in recruiting additional attentional resources during emotional interference on cognition.
Acute restraint stress prevents nicotine-induced mesolimbic dopaminergic activation via a corticosterone-mediated mechanism: A microdialysis study in the rat
2013, Drug and Alcohol Dependence
Stress affects the responsiveness to nicotine (NIC), by increasing drug use, facilitating relapse and reinstating NIC self administration even after prolonged abstinence. In turn, high corticosterone (CORT) blood levels induced by stress may alter the neurobiological properties of NIC by acting on the dopamine (DA) mesolimbic system.
In this study, we evaluated the effect of exposure to acute restraint stress on NIC-induced stimulation of the mesolimbic DA system of the rat, by studying extracellular DA levels in the nucleus accumbens shell (NAccs) with microdialysis.
NIC intravenous administration (130 μg/kg) increased DA levels in the NAccs in control rats but not in subjects exposed to stress; this latter phenomenon was prevented by blockade of CORT effects with the inhibitor of corticosterone synthesis metirapone (100 mg/kg) or the glucorticoid receptor antagonist mifepristone (150 μmol/kg).
These observations show that exposure to acute stress inhibits the stimulatory response of the mesolimbic DA system to NIC and suggest that this effect is mediated by circulating CORT acting on its receptors. These results may bear relevance in explaining the role played by stressful stimuli in NIC-seeking and taking behavior.

View all citing articles on Scopus

View full text

Lack of tolerance to nicotine-induced dopamine release in the nucleus accumbens

Abstract

European J. Pharmacol.

Biochem. Pharmacol.

Neurosci. Lett.

Pharmacol. Biochem. Behav.

Pharmacol. Biochem. Behav.

European J. Pharmacol.

Brain Res.

Pharmacol. Biochem. Behav.

Life Sci.

Nicotine and smoking: a perspective from animal studies

Psychopharmacology

Evidence that mesolimbic dopaminergic activation underlies the locomotor stimulant action of nicotine in rats

J. Pharmacol. Exp. Ther.

The effects of nicotine on locomotor activity in non-tolerant rats

Br. J. Pharmacol.

Characterization of the locomotor stimulant action of nicotine in tolerant rats

Br. J. Pharmacol.

Nicotine self-administration in rats

Br. J. Pharmacol.