Prolonged nicotine dependence associated with extended access to nicotine self-administration in rats

RationaleMost nicotine self-administration (NSA) studies in rats are performed under limited-access conditions. Few studies have examined the relationship between nicotine dependence and NSA.ObjectivesTo 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.MethodsThe 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.ResultsDaily 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.ConclusionThere 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.

[1]  J. Cryan,et al.  Bupropion enhances brain reward function and reverses the affective and somatic aspects of nicotine withdrawal in the rat , 2003, Psychopharmacology.

[2]  G. Koob,et al.  Persistent Increase in the Motivation to Take Heroin in Rats with a History of Drug Escalation , 2000, Neuropsychopharmacology.

[3]  S. Heinemann,et al.  Molecular and Cellular Aspects of Nicotine Abuse , 1996, Neuron.

[4]  A. Markou,et al.  Clozapine treatment attenuated somatic and affective signs of nicotine and amphetamine withdrawal in subsets of rats exhibiting hyposensitivity to the initial effects of clozapine , 2003, Biological Psychiatry.

[5]  D. Bertrand,et al.  Chronic Exposure to Nicotine Upregulates the Human α4β2 Nicotinic Acetylcholine Receptor Function , 2001, The Journal of Neuroscience.

[6]  M. Benwell,et al.  Desensitization of the nicotine‐induced mesolimbic dopamine responses during constant infusion with nicotine , 1995, British journal of pharmacology.

[7]  J. Lake,et al.  Rodent model of nicotine abstinence syndrome , 1992, Pharmacology Biochemistry and Behavior.

[8]  S. Matta,et al.  Self-administration in rats allowed unlimited access to nicotine , 1997, Psychopharmacology.

[9]  J R Hughes,et al.  Symptoms of tobacco withdrawal. A replication and extension. , 1991, Archives of general psychiatry.

[10]  Athina Markou,et al.  Decreased prepulse inhibition during nicotine withdrawal in DBA/2J mice is reversed by nicotine self-administration. , 2003, European journal of pharmacology.

[11]  S. Goldberg,et al.  Persistent behavior at high rates maintained by intravenous self-administration of nicotine. , 1981, Science.

[12]  Division on Earth.  Guide for the Care and Use of Laboratory Animals , 1996 .

[13]  A. Harrison,et al.  Fluoxetine Combined with a Serotonin-1A Receptor Antagonist Reversed Reward Deficits Observed during Nicotine and Amphetamine Withdrawal in Rats , 2001, Neuropsychopharmacology.

[14]  M. Jarvis,et al.  The scientific case that nicotine is addictive , 2005, Psychopharmacology.

[15]  B. J. Winer.  Statistical Principles in Experimental Design , 1992 .

[16]  K. S. Jacobs,et al.  Differential effects of response-contingent and response-independent nicotine in rats. , 2000, European journal of pharmacology.

[17]  G F Koob,et al.  Transition from moderate to excessive drug intake: change in hedonic set point. , 1998, Science.

[18]  A. Duchemin,et al.  Met-enkephalin and preproenkephalin mRNA changes in the striatum of the nicotine abstinence mouse , 2002, Neuroscience Letters.

[19]  S. Goldberg,et al.  A comparison of nicotine and cocaine self-administration in the dog: fixed-ratio and progressive-ratio schedules of intravenous drug infusion. , 1983, The Journal of pharmacology and experimental therapeutics.

[20]  A. Collins,et al.  Sensitivity to nicotine and brain nicotinic receptors are altered by chronic nicotine and mecamylamine infusion. , 1994, The Journal of pharmacology and experimental therapeutics.

[21]  A. Markou,et al.  The nicotinic antagonist methyllycaconitine has differential effects on nicotine self-administration and nicotine withdrawal in the rat. , 2001, Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco.

[22]  D. Fambrough.  Acetylcholine Receptors , 1974, The Journal of general physiology.

[23]  M. Benwell,et al.  Evidence that Tobacco Smoking Increases the Density of (−)‐[3H]Nicotine Binding Sites in Human Brain , 1988, Journal of neurochemistry.

[24]  M. Jarvik,et al.  Influencing cigarette smoking with nicotine antagonists , 2004, Psychopharmacologia.

[25]  J. Changeux,et al.  Acetylcholine receptors containing the β2 subunit are involved in the reinforcing properties of nicotine , 1998, Nature.

[26]  N. Benowitz,et al.  Suppression of nicotine intake during ad libitum cigarette smoking by high-dose transdermal nicotine. , 1998, The Journal of pharmacology and experimental therapeutics.

[27]  S. Matta,et al.  Norepinephrine Secretion in the Hypothalamic Paraventricular Nucleus of Rats during Unlimited Access to Self-Administered Nicotine: An In Vivo Microdialysis Study , 2001, The Journal of Neuroscience.

[28]  A. C. Collins,et al.  Effects of chronic nicotine infusion on tolerance development and nicotinic receptors. , 1983, The Journal of pharmacology and experimental therapeutics.

[29]  E. Donny,et al.  Nicotine self-administration in rats , 1995, Psychopharmacology.

[30]  S. Goldberg,et al.  Nicotine self-administration in rats: strain and nicotine pre-exposure effects on acquisition , 1997, Psychopharmacology.

[31]  G. Koob,et al.  Blockade of Nicotine Self-Administration with Nicotinic Antagonists in Rats , 1999, Pharmacology Biochemistry and Behavior.

[32]  T. Svensson,et al.  Behavioral manifestations of the nicotine abstinence syndrome in the rat: peripheral versus central mechanisms , 1997, Psychopharmacology.

[33]  D. Malin.  Nicotine dependence: studies with a laboratory model. , 2001, Pharmacology, biochemistry, and behavior.

[34]  A. Garvey,et al.  Urges to smoke during the first month of abstinence: relationship to relapse and predictors , 1995, Psychopharmacology.

[35]  G. Koob,et al.  Dramatic decreases in brain reward function during nicotine withdrawal , 1998, Nature.

[36]  R. Griffiths,et al.  Effects of mecamylamine on human cigarette smoking and subjective ratings , 2004, Psychopharmacology.

[37]  P P Rowell,et al.  Dose‐Response Relationship for Nicotine‐Induced Up‐Regulation of Rat Brain Nicotinic Receptors , 1997, Journal of neurochemistry.

[38]  G. Koob,et al.  Reward and somatic changes during precipitated nicotine withdrawal in rats: centrally and peripherally mediated effects. , 2000, The Journal of pharmacology and experimental therapeutics.

[39]  S. H. Ahmed,et al.  Long-lasting increase in the set point for cocaine self-administration after escalation in rats , 1999, Psychopharmacology.

[40]  G. Di Chiara,et al.  Dissociation of physical abstinence signs from changes in extracellular dopamine in the nucleus accumbens and in the prefrontal cortex of nicotine dependent rats. , 2000, Drug and alcohol dependence.

[41]  J. Hughes,et al.  Effect of dose on nicotine's reinforcing, withdrawal-suppression and self-reported effects. , 1990, The Journal of pharmacology and experimental therapeutics.

[42]  A. Markou,et al.  Increased GABA neurotransmission via administration of gamma‐vinyl GABA decreased nicotine self‐administration in the rat , 2002, Synapse.

[43]  B. Martin,et al.  Pharmacological evaluation of the antagonism of nicotine's central effects by mecamylamine and pempidine. , 1990, The Journal of pharmacology and experimental therapeutics.

[44]  R. West,et al.  Nicotine intake in young smokers: longitudinal study of saliva cotinine concentrations. , 1989, American journal of public health.

[45]  M. Lesage,et al.  Continuous nicotine infusion reduces nicotine self-administration in rats with 23-h/day access to nicotine , 2002, Pharmacology Biochemistry and Behavior.

[46]  A. Markou,et al.  Effects of repeated withdrawal episodes, nicotine dose, and duration of nicotine exposure on the severity and duration of nicotine withdrawal in rats , 2003, Psychopharmacology.

[47]  W. Corrigall,et al.  Nicotine maintains robust self-administration in rats on a limited-access schedule , 2004, Psychopharmacology.

[48]  S. Matta,et al.  Rat strain differences in nicotine self-administration using an unlimited access paradigm , 2002, Brain Research.

[49]  G. Koob,et al.  Neurobiological evidence for hedonic allostasis associated with escalating cocaine use , 2002, Nature Neuroscience.