5-HT1A RECEPTOR ACTIVATION INCREASES HIPPOCAMPAL ACETYLCHOLINE EFFLUXAND MOTOR-ACTIVITY IN THE GUINEA-PIG - AGONIST EFFICACY INFLUENCES FUNCTIONAL-ACTIVITY IN-VIVO

The effect of 5-hydroxytryptamine(1A) (5-HT1A) receptor activation on hippocampal acetylcholine (ACh) efflux measured by microdialysis and o n motor activity was determined in the guinea pig. Administration of t he 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin HBr (8-OH-DPAT) dose-dependently increased ACh efflux and motor activity. The effects of 8-OH-DPAT on ACh efflux may be mediated by activation o f 5-HT1A receptors but are unlikely to be achieved through 5-HT1A rece ptors on cholinergic nerve terminals, because administering 8-OH-DPAT through the dialysis probe had no effect. Systemic administration of t he 5-HT1A receptor partial agonists buspirone and ipsapirone produced marked increases in ACh efflux with less pronounced motor effects, whe reas ethylamino)ethyl]-8-azaspiro[4,5]-decane-7,9,dione methyl sulphon ate (MDL 73005) modestly increased ACh efflux with no effect on motor activity. MDL 73005 did not influence the 8-OH-DPAT-induced increase i n ACh efflux but attenuated the 8-OH-DPAT-induced increase in motor ac tivity. Administration of 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)buty l] piperazine HBr (NAN-190) blocked the behavioral effects of 8-OH-DPA T and attenuated the 8-OH-DPAT-induced increase in ACh. These actions of NAN-190 may be influenced by its alpha(1)-adrenoceptor antagonist p roperties, because administration of prazosin decreased ACh efflux. Th e differential actions of partial agonists influencing ACh efflux and motor activity in the guinea pig may be due to differing proportions o f spare receptors available for each response.