COMPARISON OF RELATIVE POTENCIES OF IV AND ICV ADMINISTERED 8-OH-DPATGIVES EVIDENCE OF DIFFERENT SITES OF ACTION FOR HYPOTHERMIA, LOWER LIP RETRACTION AND TAIL FLICKS

8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT)-induced temperature reduction, lower lip retraction and tail flick responses are widely u sed models of 5-HT1A receptor function. To obtain information about th e sites of receptors mediating these effects we measured these respons es, parallel over wide dose ranges after intracerebroventricular (i.c. v., 0.6-67 mu g/kg) and intravenous (i.v., 3-500 mu g/kg) administrati on. Analysis of the dose-response curves provided evidence for a 9.8-f old ratio of the potency of 8-OH-DPAT following i.c.v. compared to i.v . administration on body temperature reduction (ED(50) values are 5.1 and 50 mu g/kg, after i.c.v. and i.v. administration, respectively) an d a 2.9-fold ratio in potency for lower lip retraction (ED(50) values are 29 and 86 mu g/kg, after i.c.v. and i.v. administration, respectiv ely). 8-OH-DPAT was less potent in the induction of tail flicks than o f the other responses and had a lower potency after i.c.v. than after i.v. administration (ED(50) values, the first one extrapolated, are 52 6 and 246 mu g/kg, after i.c.v. and i.v. administration, respectively) . In addition, the i.c.v. ED(50) for temperature reduction was signifi cantly lower than those for lower lip retraction or tail flick respons es. The relative potency, that is, the ratio of i.v. and i.c.v. ED(50) was significantly higher for temperature reduction than for lower lip retraction or tail flick responses (ED(50) i.v./ED(50) i.c.v. values are 9.8, 2.9, and 0.47, respectively). These data provide evidence tha t distinct sites of action are involved in these models. Temperature r eduction is mediated mainly by postsynaptic receptors in the close vic inity of the lateral ventricle. Receptors that mediate lower lip retra ction are located more distantly in the brain, supporting previous evi dence that they are somatodendritic autoreceptors, and receptors in th e spinal cord are probably responsible for tail flick responses. (C) 1 997 Elsevier Science B.V.