Abstract
The purpose of the present study was to investigate whether brain reward function decreases during withdrawal from nicotine and methamphetamine, and whether decreased reward function is related to aversion during withdrawal from these drugs. For that purpose, male Sprague-Dawley rats were chronically infused subcutaneously with 9 mg/kg per day nicotine, or with 6 mg/kg per day methamphetamine using osmotic minipumps. In an intracranial self-stimulation (ICSS) paradigm, chronic infusion of nicotine and methamphetamine decreased the thresholds for lateral hypothalamic ICSS, whereas their antagonists, mecamylamine and haloperidol increased the ICSS thresholds in the rats treated with nicotine and methamphetamine, respectively. In a conditioned place aversion paradigm, mecamylamine and haloperidol produced place aversion in nicotine- and methamphetamine-infused rats, respectively. Interestingly, elevations in ICSS reward thresholds and place aversion during mecamylamine-precipitated nicotine withdrawal were almost the same in magnitude as those observed during haloperidol-precipitated methamphetamine withdrawal. The present study indicates that 1) brain reward function decreased during nicotine and methamphetamine withdrawal, and 2) a decrease in reward function may reflect the negative affective state (aversion) during withdrawal from nicotine and methamphetamine.
Highlights
Clinical evidence indicates that the affective signs of abstinence syndrome may be more relevant to drug craving and relapse to compulsive drug use than the somatic signs of withdrawal [1,2,3]
There was no significant effect of dose either in nicotine-infused rats (F (3, 47)=1.87, P>0.05) or in methamphetamine-infused rats (F (3, 47)=2.24, P>0.05), or treatmentdose interaction either in nicotine-infused rats (F (3, 47)=1.56, P>0.05) or in methamphetamine-infused rats (F(3, 47)=1.77, P>0.05)
The results of the current study demonstrate that chronic administration of nicotine and methamphetamine decrease intracranial self-stimulation (ICSS) reward thresholds, whereas their antagonists, mecamylamine and haloperidol increase ICSS reward thresholds and induce a Conditioned Place Aversion (CPA) in rats treated with nicotine and methamphetamine, respectively
Summary
Clinical evidence indicates that the affective signs of abstinence syndrome may be more relevant to drug craving and relapse to compulsive drug use than the somatic signs of withdrawal [1,2,3]. Acute administration of a drug of abuse decreases ICSS reward thresholds [4, 5] and this increased sensitivity to the stimulation is considered a measure of drug-induced euphoria [6]. Many studies have demonstrated elevations in ICSS reward thresholds during withdrawal from various kinds of drugs of abuse including amphetamine [9], cocaine [6], opiates [10], ethanol [11], and nicotine [12], all of which support the aforementioned hypothesis. The present study was designed to clarify whether elevations in ICSS reward thresholds are related to the negative affective state of withdrawal, focusing on two different types of psychostimulants, nicotine and methamphetamine
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