The nicotinic acetylcholine receptor antagonist mecamylamine prevents escalation of cocaine self-administration in rats with extended daily access.
BACKGROUND
Escalation from moderate to excessive drug intake is a hallmark of human addiction that can be modeled in rats by giving them longer daily access time to self-administer cocaine. Nicotine and cocaine are commonly coabused drugs in humans and recent work in animals suggests that activation of nicotinic acetylcholine receptors (nAChR) can increase cocaine self-administration.


OBJECTIVE
Determine the role of nAChR in the escalation of cocaine self-administration.


METHODS
Control rats self-administered cocaine (0.75 mg/kg/infusion) for either 1 or 6 h per day. Experimental groups had the nAChR antagonist mecamylamine (MEC) added to the cocaine solution for 5 days after the transition from short (1 h per day) to long access (6 h per day) for cocaine self-administration. After 5 days, MEC was removed from the cocaine solution.


RESULTS
Control rats and rats that received a low dose of MEC (7 microg/infusion) with cocaine increased their average hourly intake over 5 days of 6 h per day cocaine access. Rats that received a higher dose of MEC (70 microg/infusion) did not increase their intake of cocaine during 6 h access but continued to self-administer cocaine. When MEC was removed, this group showed an escalation in cocaine self-administration. MEC did not alter cocaine intake in a group that had continuous 1 h access.


CONCLUSIONS
Antagonism of nAChRs during the initial exposure to extended cocaine self-administration access time prevented escalation of, but did not eliminate, drug intake. These findings indicate that MEC-sensitive nAChRs are critical for determining cocaine intake as a function of longer access time.
Hansen
Stephen T
ST
Department of Behavioral Neuroscience, L470, Oregon Health & Science University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97239-3098, USA.
Mark
Gregory P
GP
D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000008:administration & dosage; D000818:Animals; D016739:Behavior, Addictive / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003042:Cocaine / Q000008:administration & dosage*; D004347:Drug Interactions; D007262:Infusions, Intravenous; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000502:physiology*; D012646:Self Administration; D013997:Time Factors
D000779:Anesthetics, Local; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D008464:Mecamylamine; D003042:Cocaine