EFFECT OF WAY-100135 ON THE HIPPOCAMPAL ACETYLCHOLINE-RELEASE POTENTIATED BY 8-OH-DPAT, A SEROTONIN(1A) RECEPTOR AGONIST, IN NORMAL AND P-CHLOROPHENYLALANINE-TREATED RATS AS MEASURED BY IN-VIVO MICRODIALYSIS

The mechanisms involved in the enhancement of acetylcholine (ACh) rele ase in the rat hippocampus by 8-hydroxy-2-(di-n-propylamino)tetralin ( 8-OH-DPAT), a serotonin (5-HT)(1A) receptor agonist, were investigated using in vivo microdialysis. Administration of p-chlorophenylalanine (PCPA, 300 mg/kg, i.p.), a tryptophan hydroxylase inhibitor, 3 days be fore the dialysis experiments reduced the hippocampal 5-HT content to 30% of that in saline-treated rats, but did not affect basal ACh relea se in the hippocampus. 8-OH-DPAT administered systemically (0.5 mg/kg, s.c.) or applied locally (30 mu M) into the hippocampus through the d ialysis probe significantly enhanced the release of ACh in the hippoca mpus of PCPA-treated rats to the same degree as that in saline-treated rats. Pretreatment with (+)WAY-100135 (5 mg/kg, i.p.), a selective 5- HT1A receptor antagonist, completely eliminated the enhancement of ACh release induced by locally applied 8-OH-DPAT, but only partially redu ced the effects induced by systemically administered 8-OH-DPAT, in bot h groups of rats. Systemically administered 8-OH-DPAT induced hyperloc omotion in the both saline- and PCPA-treated rats, but this was not el iminated by(+)WAY-100135. 8-OH-DPAT applied locally into the hippocamp us did not elicit hyperlocomotion in either group of rats. These resul ts suggest that the modification of endogenous 5-HT release via the 5- HT1A autoreceptor is not involved in the 8-OH-DPAT-induced increase of hippocampal ACh release, and that the increase of ACh release induced by locally applied 8-OH-DPAT involves mainly hippocampal postsynaptic 5-HT1A receptor stimulation. In addition, a possibility that subtypes of 5-HT receptors other than the 5-HT1A receptor, probably 5-HT7 rece ptor in the septum as well as postsynaptic 5-HT1A receptor in the hipp ocampus, are involved in the increased hippocampal ACh release induced by systemically administered 8-OH-DPAT is discussed. (C) 1998 Elsevie r Science Ireland Ltd. All rights reserved.