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 somatodendritic 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 terminal regions. Previous studies have shown that injecting 8-OH-DPAT into the raphe nuclei stimulates feeding, sexual behaviour, and locomotor activity, and serves as an unconditioned stimulus for inducing a conditioned place preference. This behavioural profile suggests that raphe injections of 8-OH-DPAT facilitate reward-related behaviour. The present study tested this hypothesis by investigating the effects of median raphe injections of 8-OH-DPAT on sensitivity to lateral hypothalamic (LH) self-stimulation. Frequencies required to sustain half-maximal rates of responding were determined following injection of saline or various doses of 8-OH-DPAT (0.2-5 micrograms) 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 sites were located outside the median raphe, and 8-OH-DPAT either slightly raised or failed to lower frequency thresholds. These results show that 8-OH-DPAT injected into the median raphe facilitates brain stimulation reward, and suggest that acute reductions in 5-HT neurotransmission may enhance sensitivity to rewarding stimuli. The possible interactions between 5-HT neurons and efferent systems utilizing dopamine and acetylcholine as neurotransmitters in mediating this effect are discussed.