| The globus pallidus is an important nucleus in the indirect pathway of the basal ganglia, which modulates movement in the body. It is reported that the firing rate and firing pattern of the globus pallidus neurons are directly related to parkinsonian akinesia, rigidity and resting tremor. Morphological studies have indicated that the globus pallidus receives dopamine innervation from the collaterals of nigrostriatal fibers. Different types of dopamine receptors are expressed in both the soma and fibers of the globus pallidus neurons.Object:To study the electrophysiological effects of dopamine D1 receptor agonist SKF38393 and antagonist SCH23390 on the firing rate of globus pallidus neurons in normal and parkinsonian rats, the posturing regulation as well as the expression of dopamine D1 receptors in the globus pallidus.Methods:In vivo extracellular single unit recordings, behavioral test and immunohistochemistry were used in the present study.Results:1. In electrophysiological study, total 58 globus pallidus neurons were recorded in normal rats. Micro-pressure injection of 5 mM SKF38393 increased the spontaneous firing rate in 25 pallidal neurons (basal:9.8±1.9Hz; SKF38393:14.3±2.5Hz, P<0.001). The average increase was 61.5±8.3%. In 12 out of the 58 pallidal neurons, SKF38393 decreased the spontaneous firing rate from 4.7±1.2Hz to 2.1±1.6Hz (P<0.001). The average decrease was 52.1±6.7%. In the left 21 pallidal neurons, micropressure ejection of SKF38393 did not alter the firing rate significantly (P>0.05).On the lesioned side of parkinsonian rats, local administration of 5 mM SKF38393 increased the frequency of spontaneous firing from 7.6±1.9Hz to 13.3±2.7Hz in 10 out of the 32 pallidal neurons (n=10, P<0.005). The average increase was 88.2±18.6%. In 14 out of the 32 pallidal neurons, SKF38393 decreased the spontaneous firing rate from 5.4±1.6Hz to 3.3±1.1Hz (n=14, P<0.01). The average decrease was 49.5±6.1%. In the left 8 pallidal neurons, micropressure ejection of SKF38393 did not alter the firing rate significantly (P>0.05).Furthermore, we observed the effects of SKF38393 on the firing rate of pallidal neurons on the unlesioned side of parkinsonian rats. Local administration of SKF38393 significantly increased the firing rate in 9 out of the 30 neurons recorded (basal:11.0±3.0Hz; SKF38393: 15.2±4.0Hz, n=9, P<0.01). The average increase was 43.0±6.3%. In 13 out of the 30 neurons, SKF38393 significantly decreased the firing rate from 9.4±2.5Hz to 5.3±1.7Hz (P<0.005). The average decrease was 47.1±4.8%. In the left 8 neurons, SKF38393 did not change the firing rate significantly. To identify the receptor subtype of SKF38393-induced change in firing rate, the effects of SCH23393 was investigated,Co-ejection of SCH23390 with SKF38393 blocked SKF38393-induced change in firing rate.2. In behaving rats, unilateral microinjection of SKF38393 induced significantly contralateral dystonic posture in the presence of systemic administration of haloperidol (P=0.01). SCH23390 could block SKF38393-induced anticataleptic effects.3. By using immunostaining, we observed the expression of dopamine D1 receptor in the globus pallidus. Dopamine D1 receptor positive neurons were observed in both normal and parkinsonian rats.Conclusion:The present in vivo electrophysiological studies provided evidence that activation of pallidal dopamine D1 receptor produced excitation or inhibition in the globus pallidus neurons. Behavioral studies revealed that intrapallidal microinjection of SKF38393 exerted anticataleptic effects in haloperidol rats. Finally, immunostaining showed positive expression of dopamine D1 receptors in the globus pallidus of both normal and parkinsonina rats. The present studies may provide experimental rational for the involvement of pallidal dopaminergic system in the treatment of Parkinson's disease. |
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