1. A possible coupling of the rat cerebral cortex 5-hydroxytryptamine (5HT)-1A receptors to isletactivating protein (IAP, pertussis toxin) sensitive Gi protein was investigated by studying the effects of a guanosine 5'-triphosphate (GTP) and IAP injection to the rat ventricle. 2. Scatchard analysis showed that Bmax value of the high-affinity componentin [3H]8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) binding was decreased by pretreatment with IAP. 3. GTP caused a significant decreased Bmax of the high affinity site for [3H]8-OH-DPAT binding. It was noted that the IAP suppressed the cyclic AMP production by 5HT, VIP and Forskolin. 4. These results suggest that the rat cortex 5HT-1A receptors are linked to the Gi protein. 5. After 3 weeks chronic administration of amitriptyline (5mg/kg), desipramine (5mg/kg), imipramine (5mg/kg), doxepin (5mg/kg) and trazodone (10mg/kg), the receptor binding assay was carried out on 5HT-1A receptors. 6. It was observed that all the antidepressant drugs except for imipramine increased the number of high-affinity sites of the 5HT-1A receptors in the frontal cortex. 7. These results suggested that the increase of the Bmax for the 5HT-1A receptor might be related to the effectiveness of the antidepressant drugs.