Effect of the rigid 2-aminoindano, derived from acenaphthene, on stereotyped behavior in rats. Role of brain dopaminergic system

Neurodegenerative and neuropsychiatric diseases are directly related to alterations or dysfunction of the central dopaminergic system. Among the first are Parkinson's disease (PD), tardive dyskinesia, Tourette's syndrome, Huntington's chorea (HD), and among the second, Schizophrenia (EZ), addiction, mania, depression, and eating disorders. In order to contribute to the therapeutic arsenal that allows restoring the homeostasis of central dopaminergic neurotransmission, 1-amino-6,7,8,8a-tetrahydro acenaphthene 2 hydrochloride (Ja116a) was pharmacologically evaluated by quantification of its effects on stereotyped behavior in rats. Male Sprague-Dawley rats were used and were implanted with an intracerebroventricular cannula (ICV). Compound Jall6a was ICV administered (5 mu g/5 mu L and 5 mu g/5 mu L), in the presence or absence of apomorphine (APO); haloperidol (HAL); buspirone (BUS) or ziprasidone (ZIP); or intraperitoneally (IP) (1mg/Kg) in rats treated with APO or HAL. Similarly, a group of rats was subjected to central dopaminergic denervation by 6OH-dopamine (6OHDA). The results show that Jal 16a induces a stereotypical behavior of gnawing and sniffing (extrapyramidal system) and grooming and licking (limbic system), effects that were blocked by HAL and reduced by buspirone and 6OHDA. These findings indicate that Ja116 acts mainly as a postsynaptic dopaminergic agonist, so it could be proposed as a novel drug for the treatment of neurodegenerative diseases such as Parkinson's disease.