Effects of nicotine and mecamylamine microinjections into the nucleus accumbens on ethanol and sucrose self-administration.
Nicotine (NIC) and ethanol (ETOH) are both drugs of abuse that can affect similar pathways in the central nervous system. However, the role of nicotinic processes in ETOH's reinforcing actions is unclear. Although the mesolimbic dopamine systems are known to be involved in the reinforcing effects of ETOH, the role of nicotinic receptors within the nucleus accumbens (NAc) in ETOH reinforcement has not been studied. To address this issue, adult male Long-Evans rats were initiated to self-administer ETOH (10% v/v, n = 14) using the sucrose-substitution procedure or sucrose (5% w/v, n = 8) in a 30-min operant session. They were then surgically implanted with bilateral stainless-steel guide cannulae to allow for microinjection into the core of the NAc. After recovery from surgery, presession microinjections of NIC (0.3, 3.3, 10, 30, and 60 microg/1 microl/brain) or the antagonist mecamylamine (MEC) (1, 3, 10, 30, and 60 microg/1 microl/brain) were performed prior to an ETOH or sucrose self-administration session. NIC (3.3 and 60 microg/microl) and MEC (30 microg/microl) both reduced ETOH self-administration behavior, without affecting sucrose-reinforced behavior. A reduction in the total duration of ETOH responding (termination) was also observed after either 60 microg/microl of NIC and 30 microg/microl of MEC. The lack of a clear dose-response relationship for the agonist and the antagonist indicates that the interaction between the NAc nicotinic system and ETOH self-administration is complex.
Department of Physiology and Pharmacology, Wake-Forest University School of Medicine, Winston-Salem, North Carolina, USA.
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D000109:Acetylcholine / Q000502:physiology; D000428:Alcohol Drinking / Q000503:physiopathology*; D000818:Animals; D004298:Dopamine / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology*; D008845:Microinjections; D009538:Nicotine / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000503:physiopathology; D051381:Rats; D020318:Rats, Long-Evans; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology; D012055:Reinforcement Schedule; D012646:Self Administration; D013395:Sucrose / Q000008:administration & dosage*
D011978:Receptors, Nicotinic; D013395:Sucrose; D008464:Mecamylamine; D009538:Nicotine; D000109:Acetylcholine; D004298:Dopamine