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.
Fletcher
P J
PJ
Section of Biopsychology, Clarke Institute of Psychiatry, Toronto, Ontario, Canada.
Tampakeras
M
M
Yeomans
J S
JS
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007026:Hypothalamic Area, Lateral / Q000187:drug effects / Q000502:physiology*; D007267:Injections; D008297:Male; D011903:Raphe Nuclei / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012201:Reward; D012653:Self Stimulation / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*
D017366:Serotonin Receptor Agonists; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin