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Effects of systemic and intra-nucleus accumbens 5-HT2C receptor compounds on ventral tegmental area self-stimulation thresholds in rats

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Abstract

Rationale

Serotonin 2C (5-HT2C) receptors may play a role in regulating motivation and reward-related behaviours. To date, no studies have investigated the possible role of 5-HT2C receptors in ventral tegmental area (VTA) intracranial self-stimulation (ICSS).

Objectives

The current study investigated the hypotheses that 5-HT2C receptors play an inhibitory role in VTA ICSS, and that 5-HT2C receptors within the nucleus accumbens (NAc) shell may be involved.

Methods

Male Sprague–Dawley rats were implanted with a VTA electrode and bilateral NAc shell cannulae for the experiment involving microinjections, and trained to respond for electrical self-stimulation. The systemic effects of the selective 5-HT2C receptor agonist WAY 161503 (0–1.0 mg/kg), the 5-HT1A/1B/2C receptor agonist TFMPP (0.3 mg/kg) and the selective 5-HT2C receptor antagonist SB 242084 (1.0 mg/kg) were compared using rate-frequency threshold analysis. Intra-NAc shell microinjections of WAY 161503 (0–1.5 μg/side) were investigated and compared to amphetamine (1.0 μg/side).

Results

WAY 161503 (1.0 mg/kg) and TFMPP (0.3 mg/kg) significantly increased rate-frequency thresholds (M50 values) without altering maximal response rates (RMAX values). SB 242084 attenuated the effects of TFMPP; SB 242084 had no affect on M50 or RMAX values. Intra-NAc shell WAY 161503 had no effect on M50 or RMAX values; intra-NAc amphetamine decreased M50 values.

Conclusions

These results suggest that 5-HT2C receptors play an inhibitory role in regulating reward-related behaviour while 5-HT2C receptor activation in the NAc shell did not appear to influence VTA ICSS behaviour under the present experimental conditions.

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Authors and Affiliations

  1. Centre for Neuroscience, 513 HMRC, University of Alberta, Edmonton, AB, Canada, T6G 2S2

    Dave J. Hayes & Robert Clements

  2. Centre for Neuroscience and W.G. Dewhurst Laboratory, Department of Psychiatry, 1E7.44 WMHSC, University of Alberta, Edmonton, AB, Canada, T6G 2R7

    Andrew J. Greenshaw

  3. Neurochemical Research Unit, Department of Psychiatry, 1E7.44 WMHSC Centre, University of Alberta, Edmonton, AB, Canada, T6G 2R7

    Andrew J. Greenshaw

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  1. Dave J. Hayes
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Correspondence to Andrew J. Greenshaw.

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This work was funded by the Canadian Institutes of Health Research (CIHR) (A.J.G). D.J.H. was the recipient of a postgraduate scholarship from the Natural Sciences and Engineering Research Council of Canada (NSERC).

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Hayes, D.J., Clements, R. & Greenshaw, A.J. Effects of systemic and intra-nucleus accumbens 5-HT2C receptor compounds on ventral tegmental area self-stimulation thresholds in rats. Psychopharmacology 203, 579–588 (2009). https://doi.org/10.1007/s00213-008-1404-4

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