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 D3-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.
Pharmacology Biochemistry and Behavior, Volume 68, Issue 3, March 2001, Pages 417-426