THRESHOLD OF DOPAMINE CONTENT AND D-1 RECEPTOR STIMULATION NECESSARY FOR THE EXPRESSION OF ROTATIONAL BEHAVIOR INDUCED BY D-2 RECEPTOR STIMULATION UNDER NORMO AND SUPERSENSITIVE CONDITIONS

We measured the minimum amount of endogenous dopamine (EDA), necessary for the expression of rotational behaviour induced by D-2 receptor st imulation in striatal or medial forebrain bundle (MFB) lesioned rats. We correlated these results with the minimum dose of D-1 receptor agon ists needed to substitute EDA in its permissive role for D-2 motor eff ects to take place. Rats with unilateral quinolinic acid (AQ) striatal or 6-hydroxydopamine (6-OHDA) MFB lesions were given increasing doses of the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (AMP T) in combination with a fixed dose of the D-2 receptor agonist quinpi role R-4,4a,5,6,7,8,8a,9-Octahydro-5-pyopyl-1H-pyrazolo (3,4-g)quinoli ne hydrochloride) and tested for rotational behavior. The animals were later sacrificed and striata removed; EDA ws measured by high perform ance liquid chromatography (HPLC). Rotational responses were abolished by increasing doses of AMPT inducing a stepwise depletion of EDA. EDA content and rotational behavior to D-2 stimulation showed a high degr ee of correlation. There was an abrupt reduction in rotational behavio r at dopamine levels of 50-60% of controls in both animal models. In a ddition, striatal or MFB lesioned rats which were maximally depleted o f dopamine by AMPT pretreatment received a fixed dose of quinpirole an d then challenged with increasing doses of D-1 receptor agonist SKF 38 393 nyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride). Rotational behavior was restored by SKF 38393 in both animal models i n dose-dependent fashion. Our results confirm the need for simultaneou s D-1/D-2 stimulation in the generation of rotational behavior in both animal models. Moreover, they demonstrate the existence of a threshol d level of D-1 stimulation necessary to exert its permissive role on D -2 mediated responses.