Prolonged nicotine dependence associated with extended access to nicotine self-administration in rats.
BACKGROUND
Most nicotine self-administration (NSA) studies in rats are performed under limited-access conditions. Few studies have examined the relationship between nicotine dependence and NSA.


OBJECTIVE
To determine how NSA access conditions affect NSA and the duration of nicotine dependence during abstinence, as reflected in somatic signs of withdrawal precipitated by administration of the nicotinic receptor antagonist mecamylamine.


METHODS
The effects of different NSA access conditions (zero, 1 h/5 days, 1 h/7 days and 6 h/7 days per week) and non-contingent nicotine administration on NSA and somatic signs were examined.


RESULTS
Daily NSA access (30 days) resulted in spontaneous and mecamylamine-induced somatic signs. Both daily access groups (1 h/day and 6 h/day, 7 days/week) exhibited spontaneous somatic signs on day 25 of NSA (17 h post-NSA) and sensitivity to mecamylamine up to 2 and 4 weeks of abstinence, respectively. In contrast, the 1 h/day, 5 days/week access group exhibited mecamylamine-induced somatic signs only up to 1 week of abstinence. NSA behavior was stable in rats with 1 h/day 5 days/week and 1 h/day 7 days/week access, but decreased from initially high rates in the 6 h/day 7 days/week access group, and decreased in rats receiving non-contingent nicotine. In contrast, extended cocaine self-administration access resulted in a gradual escalation in cocaine intake.


CONCLUSIONS
There was no escalation in nicotine intake with extended access conditions, unlike cocaine self-administration. Nevertheless, daily nicotine self-administration seven days per week, for either 1 or 6 h per day, was sufficient to induce long-lasting adaptations in nicotinic acetylcholine receptor activity reflected in spontaneous and antagonist-precipitated somatic signs of withdrawal, possibly reflecting aspects of nicotine dependence.
Paterson
Neil E
NE
Department of Neuropharmacology CVN-7, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Markou
Athina
A
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D003042:Cocaine / Q000008:administration & dosage; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D005731:Ganglionic Stimulants / Q000009:adverse effects*; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology / Q000627:therapeutic use; D009538:Nicotine / Q000009:adverse effects*; D018733:Nicotinic Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration / Q000379:methods / Q000523:psychology; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000209:etiology / Q000523:psychology*; D013997:Time Factors; D014029:Tobacco Use Disorder / Q000188:drug therapy / Q000209:etiology / Q000523:psychology*
D018765:Dopamine Uptake Inhibitors; D005731:Ganglionic Stimulants; D018733:Nicotinic Antagonists; D008464:Mecamylamine; D009538:Nicotine; D003042:Cocaine