Behavioural and biochemical consequences following activation of 5HT1-like and GABA receptors in the dorsal raphé nucleus of the rat.
The behavioural and biochemical response to the 5-HT1-like receptor compounds, 5-carboxamidotryptamine (5-CT), 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), buspirone and ipsapirone and the GABA agonist, muscimol, injected into the dorsal raphé nucleus (DRN) are reported. All compounds increased social interaction under high light, unfamiliar conditions and increased punished responding in a Vogel conflict test. At doses ranging from 5-25 times greater than those which were effective in these anxiety models, muscimol, 5-CT and 8-OH-DPAT induced a marked hypothermia and a flattening of body posture. Buspirone, on the other hand, failed to induce a significant reduction in core temperature or produce a marked flattening of posture in all animals, even at doses 100 times those effective in anxiety models. Following injection of muscimol, 5-CT, 8-OH-DPAT and buspirone into the dorsal raphé nucleus, all tended to reduce the 5-HIAA:5-HT ratios in the frontal cortex, hippocampus and hypothalamus. These findings, together with available electrophysiological data suggest that these behavioural responses are a consequence of a depression of the firing of cells in the dorsal raphé nucleus, with a corresponding decrease in functional activity of 5-HT in the forebrain.
Higgins
G A
GA
Glaxo Group Research Limited, Ware, Hertfordshire, U.K.
Bradbury
A J
AJ
Jones
B J
BJ
Oakley
N R
NR
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D002065:Buspirone / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D011187:Posture; D011743:Pyrimidines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D012919:Social Behavior; D013764:Tetrahydronaphthalenes / Q000493:pharmacokinetics / Q000494:pharmacology; D014018:Tissue Distribution
D014151:Anti-Anxiety Agents; D011743:Pyrimidines; D011963:Receptors, GABA-A; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D009118:Muscimol; D006897:Hydroxyindoleacetic Acid; C043077:ipsapirone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D002065:Buspirone