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Studies on the influence of nicotine infusions on mesolimbic dopamine and locomotor responses to nicotine

  • Clinical Pharmacology
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Abstract

The present study examined the effects of constant nicotine infusions on dopamine overflow in the nucleus accumbens and on locomotor activity and compared them with the changes evoked by repeated daily injections (one injection per day for 5 days) of the drug. The putative anxiolytic properties of nicotine have also been examined using the elevated plus-maze test of anxiety. Repetitive daily subcutaneous injections of nicotine (0.4 mg/kg) enhanced (P < 0.01) the overflow of dopamine evoked by a challenge dose of the drug (0.4 mg/kg) and increased (P < 0.01) its stimulatory effects on locomotor activity. The constant infusion of nicotine, at doses of 1 and 4 mg/kg per day, abolished (P < 0.05) the effects of a bolus injection of nicotine on extracellular dopamine and attenuated (P < 0.01) the enhanced locomotor response evoked by daily pretreatment with nicotine boli. The mesolimbic dopamine response to a bolus injection of nicotine was not significantly attenuated by nicotine infusions when the dose was reduced to 0.25 mg/kg per day. The locomotor responses in these rats were significantly (P < 0.05) less than those seen in the animals pretreated with nicotine injections alone but were also higher (P < 0.05) than those seen in saline-treated control rats given a bolus injection of nicotine. Neither the constant infusion (4 mg/kg per day) nor the injection of nicotine (0.4 mg/kg) evoked an anxiolytic or anxiogenic effect in the elevated plus-maze test. However, the nicotine infusions did abolish the locomotor stimulant effects of the drug in this apparatus. They also abolished the plasma corticosterone response to nicotine and attenuated the plasma corticosterone response to the maze. The data suggest that constant infusions of nicotine, at doses of 1 mg/kg per day or more, may cause desensitisation of the nicotinic receptors which mediate the stimulatory effects of the drug on mesolimbic dopamine release and locomotor activity. The data also suggest that the receptors which mediate the increase in plasma corticosterone, seen in animals given nicotine boli, may also be desensitised by nicotine infusions, and that these receptors may be implicated in the adrenocortical response to anxiogenic stimuli.

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Abbreviations

DA:

dopamine

NAcc:

nucleus accumbens

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Authors and Affiliations

  1. Department of Pharmacology and Clinical Pharmacology, University of Dundee Medical School, Ninewells Hospital, DD1 9SY, Dundee, UK

    M. E. M. Benwell, D. J. K. Balfour & L. F. Khadra

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  1. M. E. M. Benwell
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  2. D. J. K. Balfour
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  3. L. F. Khadra
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Correspondence to: M.E.M. Benwell

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Benwell, M.E.M., Balfour, D.J.K. & Khadra, L.F. Studies on the influence of nicotine infusions on mesolimbic dopamine and locomotor responses to nicotine. Clin Investig 72, 233–239 (1994). https://doi.org/10.1007/BF00189320

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  • DOI: https://doi.org/10.1007/BF00189320

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