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.

Repeated 7-OH-DPAT treatments: behavioral sensitization, dopamine synthesis and subsequent sensitivity to apomorphine and cocaine.

Male Wistar rats (250-350 g) were injected (SC) daily with the putative selective dopamine D3 receptor agonist, 7-OH-DPAT (0.01, 0.10, or 1.0 g/kg) or vehicle for 10 days. Fifteen minutes after each injection, the rats were tested for locomotor activity in photocell arenas for 20 min or 2 h. In two experiments, following this subchronic treatment, all rats received a challenge injection of apomorphine (1.0 mg/kg, SC), or cocaine (10 mg/kg, IP) on day 11, and were tested for locomotor activity. In a third experiment, dopamine synthesis in striatal and mesolimbic (nucleus accumbens-olfactory turbercle) tissue was assessed following acute or chronic 7-OH-DPAT treatments by measuring the accumulation of dihydroxyphenylalanine (DOPA) after treatment with a DOPA decarboxylase inhibitor. Major findings were as follows: a) acute 7-OH-DPAT treatment produced a dose-dependent decrease in locomotor activity; b) when tested for 2 h, the 1.0 mg/kg dose of 7-OH-DPAT produced a progressively greater increase in activity across the 10 test days (i.e., behavioral sensitization); c) subchronic treatment with 7-OH-DPAT did not result in cross-sensitization to either apomorphine or cocaine; d) acute treatment with the 1.0 mg/kg dose of 7-OH-DPAT significantly decreased dopamine synthesis in both striatal and mesolimbic regions; and e) chronic 7-OH-DPAT treatments did not affect basal dopamine synthesis in either brain region. Although the behavioral effects of 7-OH-DPAT were similar to the reported effects of the D2/D3 dopamine agonist quinpirole, the effects of repeated 7-OH-DPAT treatments differed from those of quinpirole in terms of cross-sensitization and basal dopamine synthesis. These results suggest that locomotor inhibition produced by low doses of 7-OH-DPAT is not related to dopamine autoreceptor stimulation, and the development of behavioral sensitization to high doses of 7-OH-DPAT is not due to the development of dopamine autoreceptor subsensitivity.