PMID: 9435169Jan 22, 1998Paper

gamma-Aminobutyric acidA agonists differentially augment gnawing induced by indirect-acting dopamine agonists in C57BL/6J mice

The Journal of Pharmacology and Experimental Therapeutics
E TirelliJ M Witkin

Abstract

Evidence from structure-activity, molecular biology, ligand binding and behavioral studies has suggested potential differences in the pharmacological effects of indirect dopamine agonists. Striatal dopaminergic neurotransmission is under the regulatory control of GABAergic inputs. The ability of agonists of gamma-aminobutyric acidA (GABAA) receptors to enhance stereotyped gnawing was used as a method for dissociating the pharmacological effects of indirect-acting dopamine agonists. Gnawing on corrugated cardboard was studied in C57BL/6J mice. The GABAA agonists, gaboxadol HCl (THIP) and muscimol, were not effective in augmenting gnawing in the presence of the direct-acting dopamine agonists, apomorphine, pergolide, RU 24213 or SKF 38393. In addition, THIP did not enhance the gnawing produced by cocaine, bupropion, GBR 12909 or WIN 35428. In contrast, THIP produced marked augmentation of the gnawing induced by methylphenidate, (+)-amphetamine, methamphetamine, amfonelic acid, indatraline, nomifensine, diclofensine, mazindol and GBR 12935. The qualitative differences in potentiation were not caused by differences in the maximal effect of the drugs alone, inadequate dose or routes of administration, or by differences in duration o...Continue Reading

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