sr140333b and Parkinsonian-Disorders

Substance P is an important neurotransmitter or neuromodulator in central nervous system. Morphological studies have revealed the existence of substance P and its high affinity receptor, neurokinin-1 receptor, in globus pallidus. The expression of neurokinin-1 receptor in external globus pallidus has been reported to be decreased or unchanged in parkinsonian patients. To further investigate the effects of pallidal neurokinin-1 receptor in Parkinson's disease, an in vivo extracellular recording in 6-hydroxydopamine parkinsonian rats was performed. Micro-pressure ejection of selective neurokinin-1 receptor agonist, [Sar9,Met(O2)11] substance P (0.1mM), increased the spontaneous firing rate of pallidal neurons by 9.1% on the lesioned side, which was significantly weaker than that on the unlesioned side (20.7%), and that in normal rats (30.0%). The selective neurokinin-1 receptor antagonist, SR140333B, prevented the excitatory effects induced by [Sar9,Met(O2)11] substance P. Based on the action of substance P in globus pallidus of parkinsonian rats we hypothesize that the activity of neurokinin-1 receptors in globus pallidus may be decreased under parkinsonian state. This finding may provide a rationale for further investigations into the potential of pallidal substance P system in the treatment of Parkinson's disease.

Topics: Action Potentials; Adrenergic Agents; Analysis of Variance; Animals; Behavior, Animal; Compulsive Behavior; Disease Models, Animal; Drug Interactions; Globus Pallidus; Male; Medial Forebrain Bundle; Neurons; Oxidopamine; Parkinsonian Disorders; Rats; Rats, Wistar; Substance P; Tropanes