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Differential effects of intra-midbrain raphé and systemic 8-OH-DPAT on VTA self-stimulation thresholds in rats

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Abstract

Rationale

Intra-median raphé nucleus (MRN) administration of the 5-HT1A receptor agonist 8-OH-DPAT decreases lateral hypothalamic self-stimulation thresholds and is reported to have biphasic effects following systemic administration. These experiments attempted to extend the previous findings to mesolimbic pathway self-stimulation at ventral tegmental area (VTA) electrodes.

Objectives

This study was conducted to provide comparative data for systemic and intra-dorsal raphé nucleus (DRN) and intra-MRN effects of 8-OH-DPAT on VTA self-stimulation.

Methods

Male Sprague-Dawley rats with VTA electrodes were trained to respond for electrical stimulation. Systemic and intra-midbrain raphé 8-OH-DPAT effects on rate-frequency thresholds were measured. Systemic administration of WAY 100635 was used to confirm 5-HT1A receptor mediation of 8-OH-DPAT effects.

Results

8-OH-DPAT (0.003–0.3 mg kg−1 SC) increased rate-frequency thresholds and decreased maximal response rates. WAY 100635 alone (0.0125–0.1 mg kg−1 SC) did not alter these measures. Intra-DRN and intra-MRN 8-OH-DPAT (5.0 μg) decreased rate-frequency thresholds without altering maximal response rates. Intra-DRN 8-OH-DPAT (0.1–5.0 μg) induced a slight decrease and intra-MRN 8-OH-DPAT a slight increase in locomotor activity. WAY 100635 (0.1 mg kg−1) blocked effects of 8-OH-DPAT on VTA self-stimulation.

Conclusion

These results confirm threshold-decreasing effects of intra-MRN 8-OH-DPAT and extend this to the DRN and to VTA thresholds. Monophasic dose dependent increases in VTA thresholds following systemic 8-OH-DPAT are not equivalent to reports for hypothalamic self-stimulation. Differences between studies may be attributable to stimulation site and/or differences in threshold measurement procedures. Effects of WAY 100635 in this study indicate 5-HT1A receptor mediation of these 8-OH-DPAT effects.

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Acknowledgements

This work was supported by an operating grant from the Canadian Institutes of Health Research. RC was the recipient of NSERC scholarship funding. The excellent technical assistance of David Epp is gratefully acknowledged.

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  1. K.-C. Ahn

    Present address: Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada

Authors and Affiliations

  1. W.G. Dewhurst Laboratories, Department of Psychiatry, 1E7.44 WMC University of Alberta, Edmonton, AB, Canada, T6G 2B7

    K.-C. Ahn, H. Pazderka-Robinson, R. Clements, R. Ashcroft, T. Ali, C. Morse & A. J. Greenshaw

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Correspondence to A. J. Greenshaw.

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Ahn, KC., Pazderka-Robinson, H., Clements, R. et al. Differential effects of intra-midbrain raphé and systemic 8-OH-DPAT on VTA self-stimulation thresholds in rats. Psychopharmacology 178, 381–388 (2005). https://doi.org/10.1007/s00213-004-2031-3

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