MEDIAN RAPHE INJECTIONS OF 8-OH-DPAT LOWER FREQUENCY THRESHOLDS FOR LATERAL HYPOTHALAMIC SELF-STIMULATION

The selective 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8 -OH-DPAT) reduces the activity of brain 5-HT neurons via somatodendrit ic autoreceptors located in the midbrain raphe nuclei. This action of 8-OH-DPAT results in reduced 5-HT synthesis and release of 5-HT in ter minal regions. Previous studies have shown that injecting 8-OH-DPAT in to the raphe nuclei stimulates feeding, sexual behaviour, and locomoto r activity, and serves as an unconditioned stimulus for inducing a con ditioned place preference. This behavioural profile suggests that raph e injections of 8-OH-DPAT facilitate reward-related behaviour. The pre sent study tested this hypothesis by investigating the effects of medi an raphe injections of 8-OH-DPAT on sensitivity to lateral hypothalami c (LH) self-stimulation. Frequencies required to sustain half-maximal rates of responding were determined following injection of saline or v arious doses of 8-OH-DPAT (0.2-5 mu g) into the median raphe. In four rats with accurate injection sites 8-OH-DPAT dose-dependently lowered frequency thresholds by up to 40%. In the remaining rats injection sit es were located outside the median raphe, and 8-OH-DPAT either slightl y raised or failed to lower frequency thresholds. These results show t hat 8-OH-DPAT injected into the median raphe facilitates brain stimula tion reward, and suggest that acute reductions in 5-HT neurotransmissi on may enhance sensitivity to rewarding stimuli. The possible interact ions between 5-HT neurons and efferent systems utilizing dopamine and acetylcholine as neurotransmitters in mediating this effect are discus sed.