The development of tolerance to nicotine parallels, and may be causally linked to the development of dependent smoking behavior. Understanding the mechanisms that underlie tolerance is thus an important step in understanding drug taking behavior. While it was once thought that tolerance depended exclusively on repeated drug exposure per se, it is now clear that learned associations with environmental cues that predict drug delivery can influence the tolerance process for a number of drugs. Thus chronic tolerance can include both environment-dependent and drug-dependent components. Recently, this laboratory has demonstrated that tolerance to the behavioral and endocrine effects of nicotine in rats also includes a learned component, and, that an anticipatory release of corticosterone (CORT), conditioned to environmental cues that signal drug delivery, may participate in this component of tolerance by reducing sensitivity to nicotine. Studies are planned to determine the contribution of this cue-triggered, anticipatory CORT response to the development of tolerance to the behavioral, endocrine and immunologic effects of nicotine. A method of drug delivery, intravenous infusion, will be used which increases greatly both the degree of control of drug-related cues and the temporal resolution of drug effects.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA007546-02
Application #
3214223
Study Section
Drug Abuse Clinical and Behavioral Research Review Committee (DACB)
Project Start
1992-07-01
Project End
1995-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
2
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Type
Schools of Arts and Sciences
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Donny, E C; Caggiula, A R; Rose, C et al. (2000) Differential effects of response-contingent and response-independent nicotine in rats. Eur J Pharmacol 402:231-40
McCallum, S E; Caggiula, A R; Booth, S et al. (2000) Mecamylamine prevents tolerance but enhances whole brain [3H]epibatidine binding in response to repeated nicotine administration in rats. Psychopharmacology (Berl) 150:8-Jan
McAllister-Sistilli, C G; Caggiula, A R; Knopf, S et al. (1998) The effects of nicotine on the immune system. Psychoneuroendocrinology 23:175-87
Caggiula, A R; Donny, E C; Epstein, L H et al. (1998) The role of corticosteroids in nicotine's physiological and behavioral effects. Psychoneuroendocrinology 23:143-59
Caggiula, A R; Antelman, S M; Kucinski, B J et al. (1998) Oscillatory-sensitization model of repeated drug exposure: cocaine's effects on shock-induced hypoalgesia. Prog Neuropsychopharmacol Biol Psychiatry 22:511-21
Robinson-Vanderwerf, T M; Di Pirro, J M; Caggiula, A R et al. (1997) The analgesia-enhancing component of ingested amniotic fluid does not affect nicotine-induced antinociception in naltrexone-treated rats. Pharmacol Biochem Behav 58:147-51
Caggiula, A R; Antelman, S M; Palmer, A M et al. (1996) The effects of ethanol on striatal dopamine and frontal cortical D-[3H]aspartate efflux oscillate with repeated treatment. Relevance to individual differences in drug responsiveness. Neuropsychopharmacology 15:125-32
Antelman, S M; Caggiula, A R; Kiss, S et al. (1995) Neurochemical and physiological effects of cocaine oscillate with sequential drug treatment: possibly a major factor in drug variability. Neuropsychopharmacology 12:297-306
Caggiula, A R; Epstein, L H; Perkins, K A et al. (1995) Different methods of assessing nicotine-induced antinociception may engage different neural mechanisms. Psychopharmacology (Berl) 122:301-6
Donny, E C; Caggiula, A R; Knopf, S et al. (1995) Nicotine self-administration in rats. Psychopharmacology (Berl) 122:390-94

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