Specific neurophysiological effects of systemic nicotine on neurons in the nucleus accumbens.
Extracellular recordings of single neurons within the nucleus accumbens (NAS) of halothane-anesthetized rats have revealed that systemic nicotine injections (0.5 and 1.0 mg/kg, s.c.) inhibit the action potentials of normally inactive NAS neurons, evoked by fimbria stimulation (fimbria-driven responses, n = 18). These nicotine inhibitions of fimbria-driven NAS action potentials appear to be centrally mediated because they were reversed by subsequent systemic injections of the centrally acting nicotinic acetylcholine (nAch) antagonist, mecamylamine (1.0 mg/kg, s.c., n = 6) but not by the peripherally acting nAch antagonist, hexamethonium (2.0 mg/kg, s.c., n = 6). Fimbria-driven NAS neurons were also tested with morphine (2.5 mg/kg, s.c.) in some experiments. Consistent with many past observations (Hakan et al., 1989), morphine did not affect these driven neurons. In other experiments, nicotine-induced inhibition of NAS fimbria-driven units was followed by haloperidol (0.5 mg/kg, s.c.), in attempts to reveal the possible role of dopamine in these effects. Haloperidol was successful at reversing nicotine inhibitions in only some cases (n = 2/6). Thus, the role of dopamine in these NAS responses to nicotine remains unclear. In contrast to the fimbria-driven NAS responses, spontaneously active NAS neurons were not affected by nicotine injections yet were subsequently inhibited with systemic morphine. These results suggest a specific neuropharmacological organization in the region of the nucleus accumbens that may relate to the qualitative and subjective differences in the experimental effects of different psychoactive drugs. Iontophoretic studies designed to localize further the site of these nicotine effects on NAS neurons are in progress.
Hakan
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RL
Department of Psychology, University of North Carolina at Wilmington 28401.
Hart
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Eyl
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D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D004558:Electric Stimulation; D006220:Haloperidol / Q000494:pharmacology; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D006584:Hexamethonium Compounds; D009270:Naloxone; D018738:Hexamethonium; D008464:Mecamylamine; D009538:Nicotine; D009020:Morphine; D006220:Haloperidol; D004298:Dopamine