Pharmacology Biochemistry andBehavior, Vol.41, pp. 547-550, 1992 0091-3057/92$5.00 + .00 Printed in the U.S.A. All rights reserved. Copyright© 1992PergamonPress Ltd. Catalepsy Induced by Striatal Acetylcholinesterase Inhibition With Fasciculin in Rats M. E. CASTELL6, B. BOLIOLI AND F. DAJAS l Divisibn Neuroqu[mica, Instituto de Investigaciones Biol6gicas Ciemente Estable, 11600 Montevideo, Uruguay Received 9 July 1991 CASTELL6, M. E., B. BOLIOLI AND F. DAJAS. Catalepsy induced by striatal acetylcholinesterase inhibition with fasciculin in rats. PHARMACOL BIOCHEM BEHAV 41(3) 547-550, 1992.--The acetylcholinesterase inhibitor peptide fasciculin (FAS) was bilaterally injected into the striatum of rats. Twenty-four hours after injection, animals showed a cataleptic syndrome that was potentiated by haloperidol (HAL). The catalepsy was significantly decreased by IP atropine. BiochemicaUy, only an increase of the homovaniUic acid in the striatum was found 24 h and 7 days after FAS treatment. Seven days after the intrastriatal FAS injection, there was no HAL potentiation of catalepsy, which was even lower than that of rats treated with IP HAL after intrastriatal injection of saline. Results are interpreted as showing the central role of the cholinergic system in the induction of catalepsy in the rat. Catalepsy Basal ganglia Fasciculin Cholinergic Toxin Haloperidol HVA AN akinetic state with some similarities to those seen in pa- tients with extrapyramidal disorders, catatonic schizophrenia, or after neuroleptic treatment of psychosis can be obtained in rodents after intraperitoneal haloperidol (HAL) administra- tion (11,20). This syndrome, called catalepsy, has been used as an animal model for neuroleptic-induced Parkinsonism and also as an indicator of neuroleptic antipsychotic activity. Since HAL is a dopaminergic antagonist, the dopaminergic path- ways of the basal ganglia were first related to this syndrome (5,6). Other neurotransmitter systems such as the GABAergic and glutamatergic ones have been also implicated (21,22). Fur- thermore, in the basal ganglia there is a well-known balance between two of their main neurotransmitter systems: the do- paminergic and cholinergic ones (2). Since arecoline and pilo- carpine have a synergistic effect with HAL and the effects of arecoline and HAL combined or alone are blocked by atropine sulfate, the cholinergic system has been also implicated in the induction of catalepsy (7). Nevertheless, the role of the cholin- ergic system is not as well established as the dopaminergic one since, for example, doses of pilocarpine required to induce catalepsy are very large (13). Besides, the role of the enzymes of the cholinergic pathway like acetylcholinesterase (ACHE) in the induction of catalepsy is not totally known in spite of the fact that an anticholinesterase drug such as physostigmine appears to produce catalepsy and increase neuroleptic-induced Parkinsonism (17,20). An important and recent body of data (9,19) has provided evidence that AChE is playing a noncholinergic role in the substantia nigra (SN). Since SN AChE is found in the cell bodies of the dopaminergic neurones of the nigrostriatal path- way, it is conceivable that functions other than the cholinergic one could also be responsible for the anticholinesterase- induced catalepsy in the rat. In this context, we performed bilateral intrastriatal injec- tions of a new anticholinesterase peptide, called fasciculin (FAS), that inhibits both the cholinolytic and peptidase activi- ties of AChE (4,8). We tested FAS cataleptic activity and its potentiation by HAL, as well as its blockade with atropine, a well-known anticholinergic drug, studying in all cases the biochemical effects. METHODS Animals Experiments were performed with Sprague-Dawley rats weighing 160-240 g, having food and tap water ad lib, and maintained on 12 L: 12 D cycle. Intracerebral Injection Under pentobarbital anaesthesia (60 mg/kg), rats were in- jected stereotaxically twice in each striatum according to the following coordinates (in ram): Right striatum: first- A: 1, L: Requests for reprints should be addressed to Dr. Federico Dajas, Divisi6n Neuroquimica, IIBCE, Av. Italia 3318, 11600 Montevideo, Uruguay. 547