Effects of buspirone on dopaminergic supersensitivity

The effects of buspirone treatment on dopaminergic supersensitivity induced by long-term haloperidol administration were studied; both spontaneous activity (locomotion and rearing frequencies) of rats observed in an open-field and apomorphine-induced stereotypy were used as experimental parameters. Buspirone per se (3.0 mg/kg, twice daily, for 30 days) did not produce dopaminergic supersensitivity. When buspirone was given in combination to haloperidol (2.0 mg/kg, once daily, for 30 days), it decreased the neuroleptic withdrawal symptoms as detected in open-field behavior 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. Taken together with previous behavioral results showing that buspirone reverses haloperidol-induced catalepsy, the present data suggest that buspirone coadministration may lead to important clinical advantages concerning different extrapyramidal side effects of neuroleptic treatment.Universidade Federal de São Paulo,ESCOLA PAULISTA MED,DEPT FARMACOL,BR-04023062 São Paulo,BRAZILUniversidade Federal de São Paulo,ESCOLA PAULISTA MED,DEPT FARMACOL,BR-04023062 São Paulo,BRAZILWeb of Scienc

Effects of buspirone on an animal model of tardive dyskinesia

1. the effects of buspirone were studied on an animal model of tardive dyskinesia, i.e., the quantification of orofacial dyskinesia in rats repeatedly treated with reserpine.2. Rats were co-treated with saline [SAL] or buspirone [BUS] (3.0 mg/kg, i.p., twice daily) and vehicle [VEH] or reserpine [RES] (0.1 mg/kg, s.c., once every other day) for 19 days. On the day 20, the animals were observed for quantification of the behavioral parameters of orofacial dyskinesia: tongue protrusion and vacuous chewing movements frequencies and duration of twitching of the facial musculature.3. Rats of the SAL+RES group exhibited a significant increase in the three behavioral parameters of orofacial dyskinesia relative to the rats of the SAL+VEH group. However, animals of the BUS+RES group showed only an increased frequency of vacuous chewing movements when compared to animals of the SAL+VEH group. in addition, the duration of the facial twitching was significantly decreased in the BUS+RES group in relation to rats of the SAL+RES group. There were no significant differences in the orofacial parameters between the BUS+VEH and the SAL+VEH groups.4. Because it was also verified that chronic buspirone treatment was able to increase apomorphine-induced yawning behavior, the possibility is raised that buspirone attenuates reserpine-induced orofacial dyskinesia through the development of dopamine autoreceptor supersensitivity.Universidade Federal de São Paulo, Escola Paulista Med, Dept Pharmacol, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Pharmacol, São Paulo, BrazilWeb of Scienc

Effects of herbimycin A in the pilocarpine model of temporal lobe epilepsy

Pilocarpine-induced status epilepticus (SE) causes widespread tyrosine phosphorylation in the brain. It has been postulated that this intracellular signal may mediate potentially epileptogenic changes in the morphology and physiology of particular brain regions, including the hippocampus. the present study evaluated the effects of herbimycin A, a protein tyrosine kinase (PTK) inhibitor, over the acute (during which intense biochemical and electrophysiological activation occurs) and the chronic phase (characterized by spontaneous and recurrent epileptic seizures and the presence of synaptic reorganization, e.g., mossy fiber sprouting) of the pilocarpine model of epilepsy. the administration of a single dose of 1.74 nmol of herbimycin A (i.c.v., 5 mu L) 5min after the onset of SE did not change the acute behavioral manifestation of seizures despite significantly decreasing c-Fos immunoreactivity in different areas of the hippocampus and of the limbic cortex. Herbimycin-treated animals developed spontaneous recurrent seizures, as did control animals, with a similar latency for the appearance of the first seizure and similar seizure frequency. Neo-Timm staining revealed that all animals experiencing SE, regardless of whether or not injected with herbimycin, showed aberrant mossy fiber sprouting in the supragranular region of the dentate gyrus. Herbimycin did not obviously affect neuronal cell death as evaluated in Nissl-stained sections. These results indicate that the PTK blockade achieved with the current dose of herbimycin reduced the acute c-Fos expression but failed to alter the spontaneous seizure frequency or to attenuate the morphological modifications triggered by the SE. (c) 2006 Elsevier B.V. All rights reserved.UNIFESP, EPM, Dept Physiol, BR-04023062 São Paulo, BrazilUNIFESP, EPM, Dept Physiol, BR-04023062 São Paulo, BrazilWeb of Scienc

Reserpine does not induce orofacial dyskinesia in spontaneously hypertensive rats

The nigrostriatal dopaminergic system seems to be involved in both reserpine-induced orofacial dyskinesia in normal rats and in the pathogenesis of hypertension in spontaneously hypertensive rats. in the present study, repeated reserpine administration (1.0 mg/kg, s.c., every other day, for 3 days) increased tongue protrusion and vacuous chewing frequencies as well as the duration of facial twitching in Wistar normotensive but not in spontaneously hypertensive rats. These results suggest that genetic hypertension and drug-induced orofacial movements may be inversely modulated by similar mechanisms in the nigrostriatal dopaminergic system. (C) 1998 Elsevier Science B.V. All rights reserved.Universidade Federal de São Paulo, Escola Paulista Med, Dept Farmacol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Farmacol, BR-04023062 São Paulo, BrazilWeb of Scienc

Effects of age on a new animal model of tardive dyskinesia

The effects of age were studied on a new animal model of tardive dyskinesia, i.e., the quantification of oral dyskinesia in rats repeatedly treated with reserpine. Adult and old rats received two injections of reserpine (0.5 or 1.0 mg/kg s.c.) or vehicle, separated by 48 h. One, 10, 25 and 40 days after the second injection of reserpine or vehicle, the animals were observed for quantification of the behavioral parameters of oral dyskinesia: tongue protrusion and vacuous chewing movement frequencies and duration of twitching of the facial musculature. Phenomenologically, control old rats and reserpine-treated adult animals showed very similar oral dyskinesia. When compared to control adult rats, the significant increase in tongue protrusion frequency induced by reserpine treatment was more persistent in the old rats than in the adult animals. Because it is well known that age increases the persistence of tardive dyskinesia, our data provide further support for the validation of reserpine-induced oral dyskinesia as an animal model of tardive dyskinesia. in addition, the possibility is raised that a common pathophysiological mechanism may underlie tardive dyskinesia and age- and reserpine-induced oral dyskinesia. (C) 1997 Elsevier Science Inc.Universidade Federal de São Paulo, Dept Farmacol, Escola Paulista Med, BR-04023062 São Paulo, SP, BrazilUniversidade Federal de São Paulo, Dept Farmacol, Escola Paulista Med, BR-04023062 São Paulo, SP, BrazilWeb of Scienc