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

ABSTRACT

RATIONALE Intra-median raphe nucleus (MRN) administration of the 5-HT(1A) 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 raphe 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 raphe 8-OH-DPAT effects on rate-frequency thresholds were measured. Systemic administration of WAY 100635 was used to confirm 5-HT(1A) 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 microg) decreased rate-frequency thresholds without altering maximal response rates. Intra-DRN 8-OH-DPAT (0.1-5.0 microg) 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-HT(1A) receptor mediation of these 8-OH-DPAT effects.