BRAIN ACETYLCHOLINE IS INVOLVED IN THE ACTH-INDUCED BEHAVIORAL SYNDROME IN RATS

Stretching, yawning, penile erections and excessive grooming induced in adult rats by the intracerebroventricular injection of ACTH1-24 (4-mu-g/rat) were completely abolished by pretreatment with the cholinergic neuron blocking agent, hemicholinium-3 (20-mu-g/rat i.c.v.), and significantly reduced by the non-selective muscarinic antagonist, atropine sulphate (4 mg/kg i.p.) (except for stretching). The M1-muscarinic antagonist, pirenzepine, at the dose of 80-mu-g/rat i.c.v. almost completely prevented all the above behavioral effects of ACTH, while the M3-muscarinic antagonist, 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) (25-mu-g/rat i.c.v.) had no influence, and the nicotinic antagonist mecamylamine (25 and 50-mu-g/rat i.c.v.) only reduced excessive grooming and the number of penile erections. The M2-antagonist, 11-2[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one, (AF-DX 116), inhibited stretching, yawning and grooming (but not penile erections) at low doses (1-mu-g/rat i.c.v.), while at higher doses (4 or 6-mu-g/rat i.c.v.) it inhibited penile erections but not the other ACTH-induced behaviors. It is concluded that the most typical behavioral effects of ACTH in rats involve brain cholinergic neurons and the activation mainly of central M1- and M2-muscarinic receptors.