Efeitos da buspirona em modelos animais de discinesia tardia

Abstract

In the last two centuries, the knowledgement about the central nervous systems increased enormously, making possible the treatment of patients who suffer of all sort of central nervous systems’ diseases. One of this diseases is Tardive Dyskinesia, a syndrome characterized by repetitive involuntary movements, usually involving mouth, face and tongue and sometimes limb and trunk musculature. The syndrome is considered to be an adverse effect of prolonged administration of antipsychotic drugs (normally named neuroleptics). It persists for moths after neuroleptic has been discontinued and may be irreversible (Karniol, 1979; Casey, 1985; Kane, 1995). In a recent meta-analysis study, Soares (1997) concluded that there is no efficacious therapeutic interventions for tardive dyskinesia. In this thesis, we studied the behavior effects of buspirone administration on animal models of tardive dyskinesia. These models comprised the [1] dopaminergic supersensitivity induced by long-term haloperidol administration, which is quantified by the spontaneous activity (locomotion and rearing frequency) of rats observed in an open-field or [2] by the apomorphine-induced stereotyped behavior, and [3] the quantification of orofacial dyskinesia in rats repeatedly treated with reserpine. In the first an second models, buspirone per se (3.0 mg/kg, i.p., twice daily, for 30 days) did not produce dopaminergic supersensitivity. When buspirone was given in combination to haloperidol (2.0 mg/kg, i.p., once daily, for 30 days), it decreased the neuroleptic withdrawal symptoms as detected in open-field but not in apomorphine-induced stereotypy. Although single administration of buspirone per se decreased both open-field and apomorphine-induced stereotypy behavior, buspirone single administration did not modify the acute effects of haloperidol on these two behavioral models. In the third model, rats were co-treated with saline or buspirone (3.0 mg/kg, i.p., twice daily) and vehicle or reserpine (0.1 mg/kg, s.c., once every other day) for 19 days. On the day 20, the animals were observed for the quantification of the behavioral parameters of orofacial dyskinesia: tongue protrusion and vacuous chewing movements frequencies and duration of twitching of the facial musculature. Reserpine-treated rats exhibited a significant increase in the three behavioral parameters of orofacial dyskinesia relative to the saline-treated rats. The co-administration of buspirone in the reserpine-treated rats attenuated the development of orofacial dyskinesia, when compared to the reserpine-treated rats. We also verified that chronic (30 days) buspirone treatment was able to increase apomorphine-induced yawning behavior. The possibility is raised that buspirone attenuates haloperidol-induced increased locomotion and rearing and reserpine-induced orofacial dyskinesia through the development of dopamine autoreceptor supersensitivity. Taken together with previous clinical reports, the present data suggest that buspirone co-administration may lead to important clinical effects concerning different tardive dyskinesia treatment.