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 tre atments with a low dose of the dopamine D-3-preferring receptor agonist 7-O H-DPAT would attenuate the development of behavioral sensitization to the i ndirect dopamine receptor agonist, cocaine, or the direct dopamine receptor agonist, apomorphine. In two experiments, male Wistar rats (250-350 g) wer e given seven daily injections of 7-OH-DPAT (0.05 mg/kg sc) or vehicle in c ombination with either cocaine (15 mg/kg ip), apomorphine (1.0 mg/kg sc), o r vehicle. After the injections, the rats were tested for activity in photo cell arenas for 40 min, and three measures of motor behavior (distance trav eled, rearing, and stereotypy) were recorded at 10-min intervals. A total o f 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 f ollows: (a) 7-OH-DPAT treatments alone suppressed all measures of locomotor activity and did not affect subsequent behavioral sensitivity to either co caine 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 tre atments alone increased horizontal activity and stereotypy but completely a bolished rearing behavior; (d) like cocaine, repeated treatments with apomo rphine induced behavioral sensitization; (e) concurrent treatments of 7-OH- DPAT with cocaine acutely attenuated cocaine-induced increases in motor beh avior 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 resu lts that concurrent treatment with 7-OH-DPAT does not block the development of behavioral sensitization to either cocaine or apomorphine. Moreover: th e differential acute and chronic effects of 7-OH-DPAT on cocaine- and apomo rphine-induced hyperactivity appear to be mediated by dopamine autoreceptor stimulation. (C) 2001 Elsevier Science Inc. All rights reserved.