Differential effects of 7-OH-DPAT on the development of behavioral sensitization to apomorphine and cocaine.

The primary objective of this study was to determine whether concurrent treatments with a low dose of the dopamine D(3)-preferring receptor agonist 7-OH-DPAT would attenuate the development of behavioral sensitization to the indirect dopamine receptor agonist, cocaine, or the direct dopamine receptor agonist, apomorphine. In two experiments, male Wistar rats (250-350 g) were given seven daily injections of 7-OH-DPAT (0.05 mg/kg sc) or vehicle in combination with either cocaine (15 mg/kg ip), apomorphine (1.0 mg/kg sc), or vehicle. After the injections, the rats were tested for activity in photocell arenas for 40 min, and three measures of motor behavior (distance traveled, rearing, and stereotypy) were recorded at 10-min intervals. A total of 24 h after the last preexposure session, all rats were given a challenge injection of either cocaine (10.0 mg/kg ip, Experiment 1) or apomorphine (1.0 mg/kg sc, Experiment 2) and tested for activity. Major findings were as follows: (a) 7-OH-DPAT treatments alone suppressed all measures of locomotor activity and did not affect subsequent behavioral sensitivity to either cocaine or apomorphine; (b) cocaine treatments acutely increased all measures of activity, and repeated treatments produced behavioral sensitization to the horizontal locomotor-activating effects of cocaine; (c) apomorphine treatments alone increased horizontal activity and stereotypy but completely abolished rearing behavior; (d) like cocaine, repeated treatments with apomorphine induced behavioral sensitization; (e) concurrent treatments of 7-OH-DPAT with cocaine acutely attenuated cocaine-induced increases in motor behavior but enhanced the development of behavioral sensitization to cocaine; and (f) concurrent 7-OH-DPAT treatments did not significantly affect either the acute or chronic effects of apomorphine. It is evident from these results that concurrent treatment with 7-OH-DPAT does not block the development of behavioral sensitization to either cocaine or apomorphine. Moreover, the differential acute and chronic effects of 7-OH-DPAT on cocaine- and apomorphine-induced hyperactivity appear to be mediated by dopamine autoreceptor stimulation.