Lack of CB1 cannabinoid receptors modifies nicotine behavioural responses, but not nicotine abstinence

Lack of CB1 cannabinoid receptors modifies nicotine behavioural responses, but not nicotine... Cannabis is the most widely consumed illicit drug and its consumption is currently associated with tobacco, which contains another psychoactive compound, namely nicotine. Interactions between cannabinoids and other drugs of abuse, such as opioids, have been previously reported. The aim of the present study was to evaluate the possible role of CB1 cannabinoid receptor in responses induced by acute and repeated nicotine administration by using knockout mice lacking the CB1 cannabinoid receptor and their wild-type littermates. Acute nicotine (0.5, 1, 3 and 6 mg/kg, sc) administration decreased locomotor activity and induced antinociceptive responses in the tail-immersion and the hot-plate test, in wild-type animals. The antinociceptive effects in the tail-immersion test were significantly enhanced in CB1 knockout mice. In wild-type mice nicotine (0.5 mg/kg, sc) produced a significant rewarding effect, as measured by a conditioned place preference paradigm. This response was absent in CB1 knockout mice. Finally, a model of mecamylamine-induced abstinence in chronic nicotine-treated mice (10 mg/kg/day, sc) was developed. Mecamylamine (1 and 2 mg/kg, sc) precipitated several somatic signs of nicotine withdrawal in wild-type dependent mice. However, no difference in the severity of nicotine withdrawal was observed in CB1 knockout mice. These results demonstrate that some acute effects and motivational responses elicited by nicotine can be modulated by the endogenous cannabinoid system and support the existence of a physiological interaction between these two systems. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neuropharmacology Elsevier

Lack of CB1 cannabinoid receptors modifies nicotine behavioural responses, but not nicotine abstinence

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Publisher
Elsevier
Copyright
Copyright © 2002 Elsevier Science Ltd
ISSN
0028-3908
eISSN
1873-7064
D.O.I.
10.1016/S0028-3908(02)00118-1
Publisher site
See Article on Publisher Site

Abstract

Cannabis is the most widely consumed illicit drug and its consumption is currently associated with tobacco, which contains another psychoactive compound, namely nicotine. Interactions between cannabinoids and other drugs of abuse, such as opioids, have been previously reported. The aim of the present study was to evaluate the possible role of CB1 cannabinoid receptor in responses induced by acute and repeated nicotine administration by using knockout mice lacking the CB1 cannabinoid receptor and their wild-type littermates. Acute nicotine (0.5, 1, 3 and 6 mg/kg, sc) administration decreased locomotor activity and induced antinociceptive responses in the tail-immersion and the hot-plate test, in wild-type animals. The antinociceptive effects in the tail-immersion test were significantly enhanced in CB1 knockout mice. In wild-type mice nicotine (0.5 mg/kg, sc) produced a significant rewarding effect, as measured by a conditioned place preference paradigm. This response was absent in CB1 knockout mice. Finally, a model of mecamylamine-induced abstinence in chronic nicotine-treated mice (10 mg/kg/day, sc) was developed. Mecamylamine (1 and 2 mg/kg, sc) precipitated several somatic signs of nicotine withdrawal in wild-type dependent mice. However, no difference in the severity of nicotine withdrawal was observed in CB1 knockout mice. These results demonstrate that some acute effects and motivational responses elicited by nicotine can be modulated by the endogenous cannabinoid system and support the existence of a physiological interaction between these two systems.

Journal

NeuropharmacologyElsevier

Published: Oct 1, 2002

References

  • Cannabis: pharmacology and toxicology in animals and humans
    Adams, I.B.; Martin, B.R.
  • The effects of nicotine on locomotor activity in non-tolerant rats and tolerant rats
    Clarke, P.B.S.; Kumar, R.
  • Alcohol, cannabis and tobacco use among Australians: a comparison of their associations with other drug use and use disorders, affective and anxiety disorders, and psychosis
    Degenhardt, L.; Hall, W.; Lynskey, M.
  • Behavioral manifestations of the nicotine abstinence syndrome in the rat: peripheral versus central mechanisms
    Hildebrand, B.E.; Nomikos, G.G.; Bondjers, C.; Nisell, M.; Svensson, T.H.
  • Reduced dopamine output in the nucleus accumbens but not in the medial prefrontal cortex in rats displaying a mecamylamine-precipitated nicotine withdrawal syndrome
    Hildebrand, B.E.; Nomikos, G.G.; Hertel, P.; Schilstrom, B.; Svensson, T.H.
  • The neurobiology of drug addiction
    Koob, G.F.; Nestler, E.J.
  • Cocaine, but not morphine, induces conditioned place preference and sensitization to locomotor responses in CB1 knockout mice
    Martin, M.; Ledent, C.; Parmentier, M.; Maldonado, R.; Valverde, O.
  • Lack of morphine-induced dopamine release in the nucleus accumbens of cannabinoid CB(1) receptor knockout mice
    Mascia, M.S.; Obinu, M.C.; Ledent, C.; Parmentier, M.; Bohme, G.A.; Imperato, A.; Fratta, W.
  • Nicotine-induced conditioned place preference and conditioned place aversion in mice
    Risinger, F.O.; Oakes, R.A.
  • Blockade of nicotine self-administration with nicotinic antagonists in rats
    Watkins, S.S.; Epping-Jordan, M.P.; Koob, G.F.; Markou, A.

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