Dopamine autoreceptor agonists including CGS 15855A decrease dopamine release and metabolism in mouse brain.

Abstract

The ability of dopamine autoreceptor agonists to suppress the in vivo release or metabolism of dopamine in mouse brain was determined by measuring steady state levels of 3-methoxytyramine (3-MT) or dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), respectively. These experiments provide the first neurochemical evidence for dopamine autoreceptors in the mouse. (-)N-n-propylnorapomorphine, apomorphine, (+)-3-PPP, TL-99, and the novel dopamine autoreceptor agonist CGS 15855A each decreased 3-MT levels at doses that approximated their potency in the gamma-butyrolactone model. CGS 15855A suppressed dopamine release and metabolism to the same extent in the rat and mouse neostriatum. Generally, agonist-induced decreases in 3-MT levels were obtained to a greater extent or with lower doses than were changes in DOPAC or HVA. The autoreceptor efficacy of CGS 15855A was confined to the (+) and not the (-) optical isomer. Consecutive injections of CGS 15855A did not induce an acute tolerance to its actions but instead prolonged for at least 3.5 h the suppression of dopamine metabolism and release. The release and metabolism of dopamine in mouse limbic and striatal regions is regulated by autoreceptors with a pharmacological specificity that is similar to autoreceptors of the rat.