Enhancement of cocaine-seeking behavior by repeated nicotine exposure in rats

Abstract

Rationale-Drugs with addictive liability have a high probability of co-abuse in many addicts. For example, cocaine users are several times more likely to smoke cigarettes than non-cocaine users, and smoking increases during cocaine use. Previous work has provided evidence that nicotine and cocaine have interactive neurochemical effects, particularly with regard to dopamine (DA) transmission.Objectives-The present study examined the impact of nicotine treatment on the reinforcement efficacy of self-administered cocaine and non-reinforced responding for cocaine in rats.Methods-Rats were trained to self-administer cocaine (i.v.) on a progressive ratio (PR) schedule of reinforcement. Self-administration training continued until stable responding was obtained. Acute nicotine pretreatment consisted of a subcutaneous injection (0.15, 0.3 and 0.6 mg/kg) 3 min prior to cocaine access. In the repeated treatment condition, a separate group of animals was given nicotine (0.6 mg/kg, s.c.) 3 min prior to cocaine access for 14 consecutive days. During extinction trials, these animals were injected with nicotine (0.6 mg/kg, s.c.) after 45 min of non-reinforced responding.Results-Acute nicotine treatment produced an inverted U-shaped dose-response function with lower doses increasing and the highest dose decreasing the number of cocaine infusions obtained during a session. Animals treated repeatedly with the highest dose of nicotine showed a significant increase in the number of cocaine infusions by day 8 of nicotine treatment. During extinction sessions when cocaine was not available, injections of nicotine in these animals caused a reinstatement of the previously rewarded lever-press behavior.Conclusions-These findings indicate that nicotine can facilitate cocaine reinforcement, may contribute to the transition from moderate drug-taking to an escalation of drug intake which is characteristic of addiction, and may trigger relapse.

Drug Discrimination in Methamphetamine-Trained Rats: Effects of Cholinergic Nicotinic Compounds

“…For example, nicotine has been shown to increase DA levels in the nucleus accumbens (Di Chiara, 2000) in a manner that is additive or synergistic with the effects of psychomotor stimulants (e.g., Gerasimov et al, 2000). These findings are consistent with studies documenting the involvement of dopaminergic activity in maintaining intravenous self-administration of nicotine itself (Di Chiara, 2000) and with nicotine's ability to dose-dependently increase or decrease intravenous cocaine self-administration behavior (e.g., Bechtholt and Mark, 2002). Together, these results suggest that nicotinic mechanisms can influence the behavioral and neurochemical effects of psychomotor stimulant drugs and vice versa.…”

Mecamylamine Attenuates Cue-Induced Reinstatement of Nicotine-Seeking Behavior in Rats

“…Moreover, it is interesting to note that in humans mecamylamine has been found to effectively reduce drug cue-induced cocaine craving (Reid et al, 1999). Together with the fact that there is an interaction between cigarette smoking and abuse of psychoactive drugs such as cocaine (Bechtholt and Mark, 2002;Horger et al, 1992;Kouri et al, 2001;Pich et al, 1997;Reid et al, 1998), it is suggested that mecamylamine may become a potentially effective anti-craving agent for relapse prevention for not only tobacco smoking but also cocaine and likely other psychostimulant use.…”

Relação entre o craving por tabaco e o craving por crack em pacientes internados para desintoxicação

“…Como uma estratégia bem-sucedida para o tratamento da dependência de psicoestimulantes, deve-se incluir o tratamento para dependência de nicotina, pois, por causa do papel proeminente dos receptores nicotínicos nos circuitos de recompensa de drogas 30 , o tratamento sinérgico das duas dependências (crack e tabaco) nesses pacientes aumentaria as chances de evitar uma recaída para uso do crack. Portanto, sugere-se que, para a eficácia do tratamento para dependência de crack, o usuário também deve ser motivado para a abstinência do tabaco.…”