RESUMO
The globus pallidus (GP) coordinates information processing in the basal ganglia nuclei. The contribution of nicotinic cholinergic receptors (nAChRs) to the spiking activity of GP neurons is largely unknown. Several studies have reported that the effect of nAChRs in other nuclei depends on dopaminergic input. Via in vivo single unit extracellular recordings and intranuclear drug infusions, we analyzed the effects of local activation and blockade of nAChRs in neurons of both sham and 6-hydroxydopamine (6-OHDA)-lesioned rats. In sham rats, the local application of nicotine and edrophonium (an acetylcholinesterase inhibitor) increases GP neurons spiking rate. Local application of mecamylamine, a neuronal nicotinic cholinergic antagonist, diminishes pallidal neurons spiking rate, an effect not produced by d-tubocurarine, a peripheral nicotinic cholinergic antagonist. Moreover, mecamylamine blocks the excitatory effect evoked by nicotine and edrophonium. In 6-OHDA-lesioned rats, local infusion of nicotine does not change pallidal neurons firing rate. Our results show that there is a tonic cholinergic input to the GP that increases their spiking rate through the activation of nAChRs and that this effect depends on functional dopaminergic pathways.
Assuntos
Potenciais de Ação/fisiologia , Dopamina/fisiologia , Globo Pálido/fisiologia , Receptores Nicotínicos/fisiologia , Potenciais de Ação/efeitos dos fármacos , Animais , Globo Pálido/efeitos dos fármacos , Masculino , Nicotina/farmacologia , Ratos , Ratos WistarRESUMO
We have studied the effect of the lesion of the dopaminergic innervation of the thalamic reticular nucleus (TRn) on anxiety and motor behaviour. The lesion of the dopamine innervation was produced by the injection of 6-hydroxydopamine into the dorsal part of the thalamic reticular nucleus. The lesion decreased the number of TH (+) cells of the pars compacta of substantia nigra by 33%, without modifying the number of TH (+) cells in ventral tegmental area. The lesion increased the time spent by the rats on the open arms of the elevated plus maze and decreased the duration of burying in the shock-probe test. Both results suggest reduced anxiety. The loss of the dopamine innervation to the TRn decreased the number of rearings but did not significantly affect total motor activity, gait or motor coordination, as evidenced by rotarod performance. These findings suggest that dopamine in the TRn plays a role in fear-related behaviour.
Assuntos
Ansiedade/fisiopatologia , Atividade Motora/efeitos dos fármacos , Oxidopamina/toxicidade , Núcleos Talâmicos/efeitos dos fármacos , Análise de Variância , Animais , Ansiedade/prevenção & controle , Contagem de Células/métodos , Comportamento Exploratório/efeitos dos fármacos , Comportamento Exploratório/fisiologia , Medo/efeitos dos fármacos , Medo/fisiologia , Imuno-Histoquímica , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Atividade Motora/fisiologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Oxidopamina/administração & dosagem , Ratos , Ratos Wistar , Substância Negra/efeitos dos fármacos , Substância Negra/metabolismo , Substância Negra/patologia , Núcleos Talâmicos/metabolismo , Núcleos Talâmicos/patologia , Tirosina 3-Mono-Oxigenase/metabolismo , Área Tegmentar Ventral/efeitos dos fármacos , Área Tegmentar Ventral/metabolismo , Área Tegmentar Ventral/patologiaRESUMO
There is evidence that histamine H3 receptors co-localise with dopamine D1 receptors on the terminals of striato-nigral neurones. In this work we studied the effect of the local activation of H3 receptors present in substantia nigra pars reticulata (SNr) on turning behaviour following apomorphine administration to either naive or hemiparkinsonian rats. In naive rats the intranigral (SNr) injection of the H3 receptor agonist immepip (3.2 or 32 ng/1 microl) resulted in ipsilateral turning following systemic apomorphine (0.5 mg/kg, subcutaneous). The effect of immepip was related to the dose and prevented by the H3 antagonist thioperamide (5 mg/kg, intraperitoneal). Conversely, in rats with 6-hydroxydopamine (6-OHDA) lesions to either substantia nigra pars compacta or the medial forebrain bundle (mfb), apomorphine-induced contralateral turning was reduced by intranigral immepip, an effect prevented by systemic thioperamide. Our data show that H3 receptors present in SNr regulate the synaptic output of the basal ganglia, most likely by reducing GABA release from striato-nigral terminals. These results may be relevant for the understanding of the role of histamine and H3 receptors in the control of motor behaviour both in normal and pathophysiological conditions, such as Parkinson's disease in which histaminergic innervation and histamine levels in substantia nigra have been shown to increase.