Intravenous nicotine self-administration in rats: effects of mecamylamine, hexamethonium and naloxone.
The rate and pattern of lever pressing were studied in 18 rats during 24-h sessions in which responding resulted in intravenous infusions of nicotine. There were four indications of the positive reinforcing effect of nicotine: (1) a greater number of lever presses when nicotine was response-contingent compared to when saline was available; (2) a greater number of responses on the lever resulting in an infusion of nicotine than on the control lever; (3) systematic decreases in the number of contingent nicotine infusions when nicotine was delivered noncontingently; and (4) systematic changes in the frequency of lever pressing as a function of dose. Under a fixed ratio 1 (FR 1) schedule, the number of infusions first increased and then decreased as the dose of nicotine was decreased (64, 32, 16, and 8 microg/kg infusion) and nicotine intake (mg/kg every 24 h) was directly related to the infusion dose. As the FR size was increased from 1 to 6, the number of lever presses increased and the number of infusions (32 microg/kg) remained stable. At FR values greater than 6, both the number of lever presses and infusions decreased. Presession injections of mecamylamine (0.75, 1.5, and 3.0 mg/kg, s.c.) decreased the number of infusions in a dose-related manner. Presession injections of hexamethonium (1.5 and 3.0 mg/kg, s.c.) or naloxone (0.75, 1.5, and 3.0 mg/kg, s.c.) did not alter the within- or between-session patterns of nicotine self-administration. Under the conditions of the present experiment, nicotine served as an effective reinforcer and the behavior was shown to be sensitive to both FR size and infusion dose. In addition, the results suggest that nicotine self-administration involves central nicotinic receptors and that opioid receptor antagonism has no effect on nicotine's reinforcing effects in rats.
DeNoble
Victor J
VJ
Philip Morris Research Center, Behavioral Pharmacology Laboratory, Bells Road, Richmond, VA 23284, USA. vjdfly@aol.com
Mele
Paul C
PC
D000818:Animals; D001245:Association Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018738:Hexamethonium / Q000494:pharmacology*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology*; D009538:Nicotine / Q000008:administration & dosage*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D011978:Receptors, Nicotinic / Q000187:drug effects; D011957:Receptors, Opioid / Q000187:drug effects; D012055:Reinforcement Schedule
D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D011957:Receptors, Opioid; D009270:Naloxone; D018738:Hexamethonium; D008464:Mecamylamine; D009538:Nicotine