| The globus pallidus (GP) is an important structure in the indirect pathway of basal ganglia circuit. By innervating all the other basal ganglia nuclei, the globus pallidus plays a critical role in movement regulation. It is well known that the firing rate and pattern of the globus pallidus neurons, as well as the changes of its intrinsic neurotransmitters and receptors are directly related to the manifestation of Parkinson’s disease. Previous studies have shown that the globus pallidus receives dopaminergic innervation from the collaterals of nigrostriatal fibers. There is positive expression of dopamine D2receptor in the globus pallidus in several species.Object:To study the effects of dopamine D2receptor agonist, quinpirole, on the firing rate of globus pallidus neurons in normal rats and6-hydroxydopamine (6-OHDA) parkinsonian rats, and observe the expression of dopamine D2receptor in the globus pallidus of normal and6-OHDA parkinsonian rats.Methods:In vivo extracellular single unit recordings and immunohistochemistry were used in the present study.Results:1. Total61globus pallidus neurons were recorded in normal rats. In24out of the61(39.3%) globus pallidus neurons, micro-pressure ejection of dopamine D2receptor agonist, quinpirole (5mM), increased the spontaneous firing rate from12.6±1.7Hz to18.3±2.0Hz (P<0.001). The average increase was62.7±11.2%. In another16out of the61(26.2%) globus pallidus neurons, micro-pressure ejection of quinpirole decreased the spontaneous firing rate from15.9±2.3Hz to10.0±1.4Hz (P<0.001). The average decrease was37.5±2.9%. The quinpirole-induced increase and decrease in firing rate were significantly different from that of vehicle (normal saline) injection (P<0.01). In the left21pallidal neurons, quinpirole did not alter the firing rate significantly.2. In6-OHDA lesioned rats, total47pallidal neurons were recorded and the basal spontaneous firing rate was lower than that of normal rats (P<0.05). Micro-pressure ejection of5mM quinpirole increased the spontaneous firing rate in25out of the47(53.2%) pallidal neurons from9.4±1.4Hz to14.9±2.3Hz (P<0.001), the average increase was64.2±5.6%. In11out of the47(23.4%) neurons, quinpirole decreased the spontaneous firing rate from11.4±3.1Hz to6.2±1.8Hz (P<0.001), the average decrease was51.9±6.3%. The quinpirole-induced increase and decrease in firing rate were significantly different from that of vehicle (normal saline) injection (P<0.01). In the left11pallidal neurons, quinpirole did not alter the firing rate significantly.3. On the unlesioned side, total45pallidal neurons were recorded and the basal spontaneous firing rate was not different from that of normal rats (P>0.05). Micro-pressure ejection of quinpirole (5mM) increased the firing rate in15out of the45(33.3%) pallidal neurons from9.1±.8Hz to12.4±2.2Hz (P<0.001). The average increase was71.1±9.8%. Quinpirole also decreased the firing rate from10.3±2.3Hz to6.4±1.8Hz (P<0.001) in14(31.1%) pallidal neurons. The average decrease was43.3±5.7%. The quinpirole-induced increase and decrease in firing rate were significantly different from that of vehicle (normal saline) injection (P<0.01). In the left16pallidal neurons, quinpirole did not alter the firing rate significantly.4. Positive expression of dopamine D2receptor located in the cytoplasm, cellular membrane and nerve fibers of pallidal neurons in normal rats and both the lesioned and the unlesioned sides of6-OHDA parkinsonian rats. The expression of dopamine D2receptor in the globus pallidus of lesioned side of parkinsonian rats was stronger than that in the normal rats (P<0.05). The expression of dopamine D2receptor on the unlesioned side of parkinsonian rats did not change obviously compared to that in normal rats (P>0.05).Conclusion:Electrophysiological results showed that activation of dopamine D2receptor increase or decrease the firing rate of globus pallidus neurons, respectively. Immunohistochemical staining showed that positive expression of dopamine D2receptor located in the cytoplasm, cellular membrane and nerve fibers of pallidal neurons in normal rats and both the lesioned and the unlesioned sides of parkinsonian rats. The expression of dopamine D2receptor in the globus pallidus of lesioned side of parkinsonian rats was stronger than that in the normal rats. The experimental results will provide a theoretical and experimental basis for further investigation of the pathogenesis of Parkinson’s disease and possible adjuvant treatment. |
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