The nicotinic acetylcholine receptor antagonist mecamylamine prevents escalation of cocaine self-administration in rats with extended daily access

Stephen T. Hansen, Gregory P. Mark

Research output: Contribution to journalArticle

42 Scopus citations


Rationale: 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. Objectives: 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 μg/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 μg/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.

Original languageEnglish (US)
Pages (from-to)53-61
Number of pages9
Issue number1
StatePublished - Sep 1 2007



  • Acetylcholine
  • Addiction
  • Cholinergic system
  • Escalation
  • Nicotinic receptors
  • Psychostimulant
  • Self-administration

ASJC Scopus subject areas

  • Pharmacology

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