Repeated treatments with 7-OH-DPAT: context-independent behavioral sensitization and conditioned hyperactivity.

The primary objective of this study was to determine whether the expression of behavioral sensitization to the putative dopamine D3 receptor agonist 7-OH-DPAT is context dependent. Three groups (n = 8 each) of male Wistar rats (250-350 g) were given nine injections (at 48-h intervals) of 7-OH-DPAT (1.0 mg/kg, SC) or vehicle 15 min before and after activity testing. The paired group received 7-OH-DPAT before activity testing and vehicle after testing. The unpaired group received vehicle before and 7-OH-DPAT after testing, and the vehicle control group received two vehicle injections. Locomotor activity was measured in photocell arenas for 2 h. After the first seven sessions, all rats were tested for activity following a vehicle injection to test for possible conditioning effects. Prior to the 11th session, all rats were given a challenge injection of 7-OH-DPAT (1.0 mg/kg, SC) to test for sensitization. Major findings were as follows: (a) the 7-OH-DPAT/paired group displayed a progressively greater increase in locomotor activity with repeated treatments; (b) the 7-OH-DPAT/paired group was significantly more active than either the vehicle control group or the 7-OH-DPAT/unpaired group during the vehicle test session; and (c) after the 7-OH-DPAT challenge injection, the paired and unpaired 7-OH-DPAT groups were significantly, and equally, more active than the vehicle control group. In contrast to previous findings with the D2-type dopamine agonists bromocriptine and quinpirole, these results suggest that the expression of behavioral sensitization to 7-OH-DPAT is not context dependent. Moreover, these results suggest that the apparent conditioned hyperactivity and context dependency often observed after repeated dopamine agonist treatments may not be related to the same associative and/or nonassociative mechanisms.

Effects of selective dopamine D1- and D2-type receptor antagonists on the development of behavioral sensitization to 7-OH-DPAT.

The primary objective of this study was to determine whether the development of behavioral sensitization to the putative dopamine D3 receptor agonist 7-OH-DPAT could be prevented by either selective D1-type or D2-type dopamine 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 D2-type dopamine antagonist 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 tested for locomotor activity in photocell arenas for 2 h. In the first two experiments, after seven injections, all rats were tested for activity following vehicle injections to test for possible conditioning effects. In each experiment, after the last pre-exposure session, all rats were given a challenge injection of 7-OH-DPAT (1.0 mg/kg, SC) and tested for activity. Major findings were as follows: a) 7-OH-DPAT treatments produced a progressively greater increase in locomotor activity with repeated treatment; b) concurrent treatment with eticlopride or SCH 23390 (0.1 and 0.2 mg/kg) blocked the acute locomotor-activating effects of 7-OH-DPAT across days; c) eticlopride, but not SCH 23390, completely blocked the development of behavioral sensitization to 7-OH-DPAT. Although the low dose of SCH 23390 (0.1 mg/kg) produced a partial attenuation of sensitization, the higher dose (0.2 mg/kg) of SCH 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) without 7-OH-DPAT displayed a hyperactive response to the 7-OH-DPAT challenge injection; and e) after vehicle injections, rats previously given 7-OH-DPAT, SCH 23390, or eticlopride either alone or in combination were more active than vehicle control rats. These findings suggest that the neurochemical mechanisms mediating the development of behavioral sensitization to 7-OH-DPAT may differ from those of other dopamine D2-type agonists such as quinpirole or bromocriptine. Moreover, these results demonstrate that hyperactivity responses following vehicle injections in drug-pretreated animals do not necessarily reflect conditioning mechanisms.