Behavioral interactions produced by co-administration of 7-OH-DPAT with cocaine or apomorphine in the rat

Previous research from our laboratory suggests that low doses (<0.1 mg/kg) of the dopamine (DA) D-3-preferring agonist 7-hydroxy-N,N-di-n-propyl-2-ami notetralin (7-OH-DPAT) attenuate conditioned place preference (CPP) produce d by the indirect DA agonist d-amphetamine, but enhance d-amphetamine-induc ed stereotypic behaviors. This study further examined the effects of 7-OH-D PAT on behaviors produced by the indirect DA agonist, cocaine, and the non- selective direct DA agonist, apomorphine. To examine whether 7-OH-DPAT woul d alter cocaine and apomorphine dose-response curves for motor behaviors an d CPP, 0.1 mg/kg 7-OH-DPAT was co-administered with 0-30 mg/kg cocaine and 0-3 mg/kg apomorphine. To establish place conditioning, drug injections wer e paired with one of two distinctly different compartments, whereas saline injections were paired with the other compartment. Locomotion, sniffing, or al stereotypy, and headbobbing were measured following acute and repeated d rug administration during conditioning, and place conditioning was assessed 24 h following the last conditioning day. 7-OH-DPAT enhanced cocaine- and apomorphine-induced stereotypies following repeated administration. 7-OH-DP AT also attenuated cocaine-CPP, but potentiated apomorphine-CPP. Furthermor e, 7-OH-DPAT attenuated locomotion produced by high doses of apomorphine. T he attenuation of cocaine-CPP by 7-OH-DPAT likely involves stimulation of D -2/D-3 autoreceptors in the mesolimbic pathway, whereas the potentiation of apomorphine-CPP likely involves stimulation of D-2/D-3 postsynaptic recept ors. Furthermore, it is suggested that attenuation of apomorphine-induced l ocomotion by 7-OH-DPAT likely involves stimulation of postsynaptic D-3 rece ptors in the mesolimbic pathway. Thus, if postsynaptic D-3 receptors are in volved in mediating CPP and locomotion, then stimulation of D-3 receptors m ay facilitate CPP but inhibit locomotion.