BEHAVIORAL-EFFECTS IN THE RAT OF THE PUTATIVE DOPAMINE D-3 RECEPTOR AGONIST 7-OH-DPAT - COMPARISON WITH QUINPIROLE AND APOMORPHINE

This study assessed the effects of IP injections of (+/-) 7-hydroxy-2( N,N-di-n-propylamino)tetralin (7-OH-DPAT), a dopamine agonist that has been reported to have preferential affinity for the dopamine D-3 subt ype of receptor, on four behavioural procedures in the rat. 1) spontan eous locomotion, 2) electrical self-stimulation of the ventral tegment al area (VTA), using the curve-shift procedure 3) operant responding f or food under a progressive-ratio (PR) schedule and 4) induction of st ereotypies. The effects of (+/-) 7-OH-DPAT were compared to the effect s of apomorphine, a non-specific DA agonist, and quinpirole, a selecti ve D-2/D-3 agonist. All three dopamine agonists decreased locomotor ac tivity at low doses (0.01-0.3 mg/kg), and only apomorphine had clear l ocomotor stimulant effects at the highest dose tested (3 mg/kg). The t hree drugs dose-dependently depressed VTA self-stimulation in a simila r way, with low doses inducing a fairly parallel rightward shift of th e frequency/rate curves and higher doses flattening the curves. In con trast, responding for food under the PR schedule appeared to be differ entially affected by the three agonists: 7-OH-DPAT induced a biphasic effect, with a maximal decrease in lever-pressing at 0.1 mg/kg, follow ed by a return to baseline levels with increasing doses (0.3-3 mg/kg); quinpirole showed a tendency to decrease responding over the whole do se-range tested with a maximal effect of about 50% of baseline between 0.25 and 1 mg/kg, and apomorphine dose-dependently decreased respondi ng, with rats ceasing to respond at 0.3 mg/kg. All three DA agonists i nduced stereotypies, but there was a difference in the maximal stereot ypy score induced by each of the ligands: 7-OH-DPAT produced a lower m aximal effect than quinpirole or apomorphine. This indicates that each of the three dopamine agonists preferentially induced different types of stereotypies.