ergoline and isoteolin

The release of acetylcholine (ACh) from the hippocampus of freely moving rats was studied after the systemic and local administration of the 5-HT agonist chlorophenylpiperazine (mCPP), utilising the in vivo microdialysis coupled to HPLC. Intraperitoneally (i.p.) given mCPP at a dose of 8 mg kg(-1)increased the release of ACh from the hippocampus by approximately 96%. This effect was not observed when the agonist was delivered locally through the dialysis tube (reverse dialysis). The mCPP-induced increase of ACh release was prevented by i.p. mesulergine, a 5-HT2A/2C receptor antagonist, at a dose of 2 mg kg(-1). A similar effect was found with the i.p. administration of isoteoline-a putative serotonergic antagonist. Both mesulergine and isoteoline have been shown to prevent also the mCPP-induced increase of ACh release from rat cortex. In the cortex experiments both antagonists were inactive by themselves. In the hippocampus, however, isoteoline, unlike mesulergine, increased significantly the output of ACh when used alone. This effect was haloperidol-sensitive, which implies a possible dopaminergic mechanism. The results of the present work suggest that (i) the effect of mCPP on ACh release could be attributed to stimulation of 5-HT2C receptors located outside the hippocampus and (ii) isoteoline antagonizes this mCPP-induced effect irrespective of its own enhancing action on ACh release.

Topics: Acetylcholine; Animals; Aporphines; Dopamine Antagonists; Dose-Response Relationship, Drug; Drug Administration Routes; Ergolines; Haloperidol; Hippocampus; Male; Piperazines; Rats; Rats, Wistar; Receptor, Serotonin, 5-HT2C; Receptors, Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists

The changes in acetylcholine (ACh) release from the cortex of freely moving rats after systemic administration of chlorophenylpiperazine (mCPP), a 5-HT2C agonist, were measured utilising microdialysis coupled to high performance liquid chromatography. mCPP administered intraperitoneally (i.p.) increased cortical ACh release, but failed to do so when applied locally in the cortex. The effect of i.p. administered mCPP on cortical ACh release was prevented by i.p. injection of mesulergine, a 5-HT2A/2C receptor antagonist, and isoteoline, a compound previously shown to antagonize behavioural effects of mCPP. An increase of cortical ACh release was also found after the local administration of mCPP in nucleus basalis magnocellularis (NBM). The results of the present work suggest that 5-HT2C receptors located in NBM are involved in the modulation of cortical ACh release in the rat.

Topics: Acetylcholine; Animals; Antihypertensive Agents; Aporphines; Cerebral Cortex; Ergolines; Male; Microdialysis; Piperazines; Rats; Rats, Wistar; Receptors, Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists; Substantia Innominata