Effects of selective dopamine D-1- and D-2-type receptor antagonists on the development of behavioral sensitization to 7-OH-DPAT

The primary objective of this study was to determine whether the developmen t of behavioral sensitization to the putative dopamine D-3 receptor agonist 7-OH-DPAT could be prevented by either selective D-1-type or D-2-type dopa mine receptor antagonists. In three experiments, male Wistar rats (250-350 g) were given seven to nine injections (at 48-h intervals) of 7-OH-DPAT (1. 0 mg/kg, SC) or vehicle in combination with the D-2-type dopamine antagonis t eticlopride (0.3 mg/kg, SC), the D1-type dopamine antagonist SCH 23390 (0 .1 or 0.2 mg/kg, SC), or vehicle. After the injections, the rats were teste d for locomotor activity in photocell arenas for 2 h. In the first two expe riments, after seven injections, all rats were tested for activity followin g vehicle injections to test for possible conditioning effects. In each exp eriment, after the last pre-exposure session, all rats were given a challen ge injection of 7-OH-DPAT (1.0 mg/kg, SC) and tested for activity. Major fi ndings were as follows: a) 7-OH-DPAT treatments produced a progressively gr eater increase in locomotor activity with repeated treatment; b) concurrent treatment with eticlopride or SCH 23390 (0.1 and 0.2 mg/kg) blocked the ac ute locomotor-activating effects of 7-OH-DPAT across days; c) eticlopride, but not SCH 23390, completely blocked the development of behavioral sensiti zation to 7-OH-DPAT. Although the low dose of SCH 23390 (0.1 mg/kg) produce d a partial attenuation of sensitization, the higher dose (0.2 mg/kg) of SC H 23390 appeared to augment, rather than block, sensitization to 7-OH-DPAT; d) rats previously treated with SCH 23390 (0.2 mg/kg, but not 0.1 mg/kg) w ithout 7-OH-DPAT displayed a hyperactive response to the 7-OH-DPAT challeng e injection; and e) after vehicle injections, rats previously given 7-OH-DP AT, SCH 23390, or eticlopride either alone or in combination were more acti ve than vehicle control rats. These findings suggest that the neurochemical mechanisms mediating the development of behavioral sensitization to 7-OH-D PAT may differ from those of other dopamine D-2-type agonists such as quinp irole or bromocriptine. Moreover these results demonstrate that hyperactivi ty responses following vehicle injections in drug-pretreated animals do not necessarily reflect conditioning mechanisms.