Effects of behaviorally active doses of thyrotropin-releasing hormone and its analog MK-771 on dopaminergic neuronal systems in the brain of the rat.
The effects of thyrotropin-releasing hormone (TRH) and an analog of this hormone, MK-771, were determined on body shaking behavior and on biochemical estimates of the activity of dopamine (DA) neurons in the rat. Both compounds elicited dose-related episodes of "wet-dog shakes". A dose of TRH (20 mg/kg, i.p.) which caused marked shaking behavior did not alter the steady-state concentration of DA in any brain region, but, after an injection of alpha-methyltyrosine did enhance the rate of decline of DA in the nucleus accumbens, but not in the striatum of olfactory tubercle. The same dose of TRH increased the concentration of dihydroxyphenylacetic acid selectively in the nucleus accumbens, and caused a marked increase in the rate of synthesis of DA (accumulation of DOPA after the administration of a decarboxylase inhibitor) in the nucleus accumbens, and a modest and inconsistent increase in the striatum and olfactory tubercle. A single injection of MK-771 (3-100 mg/kg, i.p.) failed to change the rate of synthesis of DA in any brain region, while two injections of this compound (20 mg/kg, i.p.) slightly increased the rate of synthesis of DA in the striatum. These results suggest that TRH selectively increases the activity of DA neurons which terminate in the nucleus accumbens whereas its synthetic analog, MK-771, lacks this property. Since both compounds elicit similar body shaking behavior, it would appear that this behavior is not causally related to the actions of TRH on mesolimbic DA neurons which terminate in the nucleus accumbens.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008032:Limbic System / Q000187:drug effects; D008297:Male; D008636:Mesencephalon / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects*; D013378:Substantia Nigra / Q000187:drug effects; D053778:Thiazolidines; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology*
D011954:Receptors, Dopamine; D053778:Thiazolidines; D015102:3,4-Dihydroxyphenylacetic Acid; D013973:Thyrotropin-Releasing Hormone; D004295:Dihydroxyphenylalanine; C021597:pyro(l-alpha-aminoadipyl)-L-histidyl-L-thiazolidine-4-carboxamide; D004298:Dopamine