Neurochemical and behavioral correlates of unilateral striatal acetylcholinesterase inhibition by fasciculin in rats.

Fasciculin 2 (FAS) an anticholinesterase peptide isolated from the venom of the Green mamba (Dendroaspis angusticeps) was injected into the right striatum of albino rats (1.5 micrograms total amount). The inhibition of acetylcholinesterase (AChE) activity was 86 and 60% 24 h and 7 days after FAS injection, respectively. The treatment with apomorphine (APO) (2 mg/kg s.c.) 24 h after FAS provoked a moderate circling towards the lesioned side that was reverted by atropine (30 mg/kg i.p.). The same dose of APO 7 days after FAS, provoked an inconstant contralateral circling. Neither dopamine nor serotonin nor their metabolites were significantly affected 24 h or 7 days after FAS injection. Radioligand binding assays of dopamine, muscarinic and benzodiazepine receptors only showed a decrease of the density of the muscarinic ones 7 days after FAS. These results are interpreted as showing that the changes provoked by FAS would be compensated but the system would remain in an unsteady state only demonstrable after pharmacological challenge. The chronic down-regulation of muscarinic receptors would compensate the increased cholinergic activity and would therefore block its behavioral expression.