Somatostatin modulates the behavioral effects of dopamine receptor activation in parkinsonian rats.
Somatostatin may play a role in several neuropsychiatric disorders, including Parkinson's disease. Although functional interactions between somatostatinergic and dopaminergic transmitter systems have been well documented, no study has been conducted in animals with experimental Parkinsonism to explore the effects of somatostatin on dopamine receptor-mediated behavior. In the present study, rats with unilateral 6-hydroxydopamine-induced destruction of the medial forebrain bundle were assessed following administration of the dopamine(1/2) receptor agonist apomorphine. Ipsilateral intrastriatal infusion of somatostatin produced a dose-related inhibition of apomorphine-induced rotations with maximal effect at a dose of 7.5 microg in 2 microl. This inhibitory effect of somatostatin was antagonized by the somatostatin antagonist cyclo-somatostatin (0.1 microg in 2 microl, intrastriatally). Neither somatostatin (up to 15 microg in 2 microl) nor cyclo-somatostatin on its own induced rotations; similarly, this dose of cyclo-somatostatin did not affect apomorphine-induced rotations. From these results we suggest that exogenous somatostatin, by directly acting on its specific receptors in the striatum, inhibits the effects of dopamine receptor activation in parkinsonian rats. We conclude that therapies based on modulation of somatostatin may be worth exploring in the management of Parkinson's disease and other disorders of the basal ganglia.
Lu
J Q
JQ
Pacific Parkinson's Research Centre, Vancouver Hospital and Health Sciences Centre, University of British Columbia, Vancouver, BC, Canada.
Stoessl
A J
AJ
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001345:Autoradiography; D001522:Behavior, Animal / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000032:analysis / Q000096:biosynthesis; D009419:Nerve Tissue Proteins; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D013004:Somatostatin / Q000008:administration & dosage / Q000494:pharmacology*
D018491:Dopamine Agonists; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011954:Receptors, Dopamine; D013004:Somatostatin; D016627:Oxidopamine; D001058:Apomorphine