June 2009, Volume 204, Issue 3, pp 541-549,
Open Access This content is freely available online to anyone, anywhere at any time.
Date: 25 Feb 2009
Anxiolytic effects of nicotine in a rodent test of approach–avoidance conflict
Nicotine has been reported to produce both anxiolytic and/or anxiogenic effects in humans and animals.
This study examined whether pretreatment with nicotine would alter anxiety in a unique runway model of approach–avoidance conflict.
Materials and methods
Food-restricted rats were trained to run a straight alley once a day to obtain food upon goal-box entry. Beginning on trial 11, food reward was followed by a series of five foot shocks (0.3–0.4 mA, 0.5 s) in the goal box. Non-shocked control rats continued to run for food only. The resulting association of the goal box with both a positive (food) and negative (foot shock) stimulus produced an approach–avoidance conflict (subjects exhibited “retreat behaviors” in which they would approach the goal box, stop, and then retreat back towards the start box). Once retreats were established, their sensitivity to nicotine pretreatment (0.0, 0.03, 0.045, 0.06, or 0.075 mg/kg, i.v.) was compared to saline. In subsequent tests, the effects of nicotine (0.06 or 0.03 mg/kg) were examined on spontaneous activity (locomotion) and center-square entries in an open field (anxiety).
Doses of 0.06 and 0.075 mg/kg, but not lower doses of nicotine, reduced the number of runway retreats, and 0.06 mg/kg nicotine increased the number of open-field center entries relative to saline. No effects on locomotion were observed.
Nicotine reduced approach–avoidance conflict and increased the rats’ willingness to enter the center of an open field, suggesting that the drug can produce anxiolytic properties and that such effects may serve as an important factor in the persistence of smoking behavior.
Baker TB, Brandon TH, Chassin L (2004) Motivational influences on cigarette smoking. Ann Rev Psychol 55:463–491CrossRef
Biala G, Budzynska B (2006) Effects of acute and chronic nicotine on elevated plus maze in mice: involvement of calcium channels. Life Sci 30:81–88CrossRef
Biala G, Kruk M (2008) Calcium channel antagonists suppress cross-tolerance to the anxiogenic effects of d-amphetamine and nicotine in the mouse elevated plus maze test. Prog Neuropsychopharmacol Biol Psychiatry 1:54–61CrossRef
Brioni JD, O’Neill AB, Kim DJB, Decker MW (1993) Nicotinic receptor agonists exhibit anxiolytic-like effects on the elevated plus-maze test. Eur J Pharmacol 283:1–8CrossRef
Clarke PB, Kumar R (1983) The effects of nicotine on locomotor activity in non tolerant and tolerant rats. Br J Pharmacol 78:329–337PubMed
De noble VJ, Mele PC (2006) Intravenous nicotine self-administration in rats: effects of mecamylamine, hexamethonium and naloxone. Psychopharmacology 184:266–272CrossRef
Foulds J, Stapleton JA, Bell N, Swettenham J, Jarvis MJ, Russell MA (1997) Mood and physiological effects of subcutaneous nicotine in smokers and never-smokers. Drug Alcohol Depend 14:105–115CrossRef
Geller I, Kulak JT Jr, Seifter J (1962) The effects of chlordiazepoxide and chlorpromazine on a punishment discrimination. Psychopharmacologia 31:374–385CrossRef
Goldberg SR, Spealman RD (1983) Suppression of behavior by intravenous injections of nicotine or by electric shock in Squirrel monkeys: effects of chlordiazepoxide and mecamylamine. J Pharmacol Exp Ther 224:334PubMed
Houser VP (1978) The effects of drugs on behavior controlled by aversive stimuli. In: Blackman DE, Sanger DJ (eds) Contemporary research in behavioral pharmacology. Plenum, New York, pp 69–157
Hughes JR, Gust SW, Skoog K, Keenan RM, Fenwick JW (1991) Symptoms of tobacco withdrawal. A replication and extension. Arch Gen Psychiatry 48:52–59PubMed
Irvine EE, Cheeta S, File SE (1999) Time-course of changes in the social interaction test of anxiety following acute and chronic administration of nicotine. Behav Pharmacol 10:691–697PubMed
Kassel JD, Paronis CA, Stroud LR (2003) Smoking, stress, and negative affect: correlation, causation, and context across stages of smoking. Psycholl Bull 129:270–304CrossRef
McKennell AC (1970) Smoking motivation factors. Br J Soc Clin Psychol 9:8–22PubMed
Miller NE (1944) Experimental studies of conflict. In: Hunt J McV (ed) Personality and the behavior disorders. Ronald, New York, pp 431–465
Montgomery KC (1955) The relation between fear induced by novel stimulation and exploratory behavior. J Comp Physiol Psvchol 48:254–260CrossRef
U.S. Department of Health and Human Services (1988) The health consequences of smoking: nicotine addiction. A report of the Surgeon General. Office on Smoking and Health, Maryland
Vaidya AH, Rosenthal DI, Lang W, Crooke JJ, Benjamin D, Ilyin SE, Reitz AB (2005) Oral buspirone causes a shift in the dose–response curve between the elevated-plus maze and Vogel conflict tests in Long–Evans rats: relation of brain levels of buspirone and 1-PP to anxiolytic action. Methods Find Exp Clin Pharmacol 27:245–255PubMedCrossRef
Watkins SS, Epping-Jordan MP, Koob GF, Markou A (1999) Blockade of nicotine self-administration with nicotinic antagonists in rat. Pharmacol Biochem Behav 60:743–751CrossRef
- Anxiolytic effects of nicotine in a rodent test of approach–avoidance conflict
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