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Varenicline attenuates cue-induced relapse to alcohol, but not nicotine seeking, while reducing inhibitory response control.

Abstract：

RATIONALE:Treatment of the most widely abused drugs, nicotine and alcohol, is hampered by high rates of relapse. Varenicline tartrate, an α4β2 nicotinic receptor partial agonist, is currently prescribed as a smoking cessation aid. However, there is emerging evidence that it may also modulate alcohol seeking and cognitive functioning in rats. OBJECTIVES:As preclinical data on alcohol taking and relapse are limited, we used a self-administration-reinstatement model to evaluate the effects of varenicline on operant responding for alcohol (12%, v/v), intravenous nicotine (40 μg/kg/inf.), sucrose (10%, w/v) and on cue-induced relapse to alcohol and nicotine seeking in rats. At the cognitive level, we assed varenicline's effects on 5-choice serial reaction time task (5-CSRTT) performance with a focus on correct responses (attention) and premature responding (impulsivity), modalities that have previously been associated with addictive behaviour. RESULTS:Varenicline, at doses of 1.5 and 2.5 mg/kg, reduced alcohol and nicotine self-administration and enhanced operant responding for sucrose. At these doses, varenicline reduced cue-induced relapse to alcohol, but not nicotine seeking. In contrast, at 0.5 mg/kg, varenicline facilitated cue-induced nicotine seeking. Similar to nicotine, varenicline increased premature responding at low doses, but had no effect on any of the other behavioural parameters in the 5-CSRTT. CONCLUSIONS:Our data indicate that varenicline specifically reduced responding for nicotine and alcohol, but not for natural reinforcers such as sucrose. Interestingly, varenicline strongly attenuated cue-induced relapse to alcohol seeking, but not nicotine seeking. Varenicline may therefore be a promising aid in the treatment of alcohol addiction.

journal_name

Psychopharmacology (Berl)

journal_title

Psychopharmacology

authors

Wouda JA,Riga D,De Vries W,Stegeman M,van Mourik Y,Schetters D,Schoffelmeer AN,Pattij T,De Vries TJ

doi

10.1007/s00213-011-2213-8

subject

Has Abstract

pub_date

2011-07-01 00:00:00

pages

267-77

issue

eissn

0033-3158

issn

1432-2072

journal_volume

216

pub_type

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Varenicline attenuates cue-induced relapse to alcohol, but not nicotine seeking, while reducing inhibitory response control.