PHARMACOLOGICAL PROFILE OF DOPAMINE RECEPTOR AGONISTS AS STUDIED BY BRAIN DIALYSIS IN BEHAVING RATS

  • 1 April 1988
    • journal article
    • research article
    • Vol. 245  (1) , 257-264
Abstract
Using the technique of brain dialysis in freely moving rats we have investigated the effect of various dopamine (DA) receptor agonists on the release and metabolism of DA in two terminal dopaminergic areas, the nucleus accumbens and the dorsal caudate. Low doses of various DA receptor agonists such as apomorphine (12-100 .mu.g/kg s.c.), LY 171555 (5-50 .mu.g/kg s.c.), pergolide (5-25 .mu.g/kg s.c.), (+)-3PPP (0.5-2.5 mg/kg s.c.) and BHT 920 (10-250 .mu.g/kg s.c.) reduce DA release and elicit hypomotility. The potency of the drugs and their effectiveness is similar in the two areas. Inhibition of DA release appears related to the ability of the various agonists to stimulate D-2 rather than D-1 receptors. Thus, the reportedly selective D-1 agonist, SKF 38393, was inactive on DA release and metabolism even at doses fully active in eliciting D-1-mediated effects (grooming); on the other hand apomorphine, a D-1/D-2 agonist, and pergolide, a D-2 agonist with rather weak D-1 activity, reduced DA release in a manner which was related to their agonist activity at D-2 receptors; finally LY 171555, (+)-3PPP and BHT 920, which selectively stimulate D-2 receptors, were fully active at reducing DA release in vivo. Apomorphine, pergolide, LY 171555 and (+)-3PPP given at higher doses elicited behavioral stimulation. In contrast, BHT 920 failed to do so. In further contrast (-)-3PPP (0.1-10 mg/kg s.c.), which failed to reduce DA release at low doses, actually stimulated it at high doses (10 mg/kg s.c.) and elicited hypomotility, thus resembling DA receptor antagonists. These results indicate that brain dialysis in freely moving rats can distinguish between full DA agonists active on pre- and postsynaptic D-2 receptors (apomorphine, LY 171555, pergolide and (+)-3PPP), from agonists preferentially acting on DA autoreceptors (BHT 920) and from partial D-2 agonists with such low intrinsic activity to behave in vivo as DA antagonists ((-)-3PPP).