RESUMEN
OBJECTIVES: We examined the effects of two dopamine agonists, cabergoline and rotigotine, on tacrine-induced tremor and c-Fos expression in rats. METHODS: Rats received intraperitoneal injection of cabergoline (0.5, 1.0, or 5.0mg/kg), rotigotine (1.0, 2.5, or 10.0mg/kg), or vehicle 30min before intraperitoneal injection of tacrine (5.0mg/kg). The number of tremulous jaw movements (TJMs) after tacrine administration was counted for 5min. Animals were sacrificed 2h later under deep anesthesia, and the brain sections were immunostained in order to evaluate the c-Fos expression. RESULTS: Induction of TJMs by tacrine was dose-dependently reduced by pretreatment with cabergoline and rotigotine. The number of c-Fos-positive cells was significantly enhanced in the medial striatum, nucleus accumbens core, and nucleus accumbens shell after tacrine administration, and the enhanced expression of c-Fos in these three regions was significantly attenuated by cabergoline, while rotigotine suppressed c-Fos expression in two regions except the nucleus accumbens core. CONCLUSIONS: These results suggest that tacrine-induced TJMs would be relieved by either cabergoline or rotigotine and that anticholinesterase-induced TJMs and the ameliorating effects of dopamine agonists would relate to neuronal activation in the striatum and nucleus accumbens.
Asunto(s)
Agonistas de Dopamina/farmacología , Ergolinas/farmacología , Maxilares/fisiopatología , Tacrina/antagonistas & inhibidores , Tetrahidronaftalenos/farmacología , Tiofenos/farmacología , Temblor/tratamiento farmacológico , Temblor/fisiopatología , Animales , Cabergolina , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Relación Dosis-Respuesta a Droga , Maxilares/efectos de los fármacos , Masculino , Núcleo Accumbens/efectos de los fármacos , Núcleo Accumbens/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Tacrina/efectos adversos , Temblor/inducido químicamenteRESUMEN
We previously reported that a unilateral 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease showed allodynia-like withdrawal response to mechanical stimulation of the ipsilateral side of the rat hindpaw. The goal of this study was to investigate the effect of intrastriatal grafts of fetal ventral mesencephalon (VM) on the withdrawal response in 6-OHDA rats. The withdrawal threshold in response to the mechanical stimulation of the rat hindpaw was measured using von Frey filaments. In the ipsilateral side of the 6-OHDA lesions, the withdrawal threshold in response to mechanical stimulation significantly increased in 6-OHDA rats with VM grafts compared with those with sham grafts, but did not change in the contralateral side at 5 weeks after transplantation. The present results suggest that the intrastriatal grafts of fetal VM may relieve pain sensation induced by mechanical stimulation in 6-OHDA rats.
Asunto(s)
Cuerpo Estriado/cirugía , Hiperalgesia/fisiopatología , Mesencéfalo/trasplante , Enfermedad de Parkinson/fisiopatología , Animales , Trasplante de Tejido Fetal , Masculino , Oxidopamina , Enfermedad de Parkinson/etiología , Enfermedad de Parkinson/cirugía , Estimulación Física , Ratas Wistar , TactoRESUMEN
To clarify the psychopharmacological profile of blonanserin, a novel antipsychotic, we examined its effect on the methamphetamine-induced disruption of latent inhibition (LI) and the neural activation related to this effect in rats. To evaluate the LI, we used a conditioned emotional response in which a tone (conditioned stimulus) was paired with a mild foot shock (unconditioned stimulus). This paradigm was presented to rats licking water. Methamphetamine-induced (1.0mg/kg, i.p.) disruption of LI was significantly improved by the administration of a higher dose (3.0mg/kg, i.p.) of blonanserin and tended to be improved by 1.0-mg/kg blonanserin and 0.2-mg/kg haloperidol but not by a lower dose (0.3mg/kg) of blonanserin. Immunohistochemical examination showed blonanserin (3.0mg/kg, i.p.) increased c-Fos expression in the shell area but not in the core area of the nucleus accumbens while methamphetamine (3.0mg/kg, i.p.) produced the opposite expression pattern. Blonanserin also increased the number of c-Fos expressions in the central amygdala nucleus but not in the basolateral amygdala nucleus or the prefrontal cortex. Blonanserin ameliorates the methamphetamine-induced disruption of LI, as other antipsychotics do, and a neuronal activation and/or modulation of neurotransmission in the nucleus accumbens is related to the disruption of LI by methamphetamine and to its amelioration by blonanserin.