Repeated quinpirole treatments produce neurochemical sensitization and associated behavioral changes in female hamsters

Rationale Repeated stimulation of dopaminergic pathways with dopamine receptor agonists can produce both neurochemical and behavioral sensitization. Objectives The present study was designed to examine whether repeated treatment with the D-2-like dopamine receptor agonist, quinpirole, would produce neurochemical sensitization of D-1 dopamine receptor-mediated processes and associated behavioral changes in female hamsters in a manner analogous to that previously used to sensitize heterologous dopamine signaling pathways in derived cell lines. Materials and methods Female hamsters received two injections of quinpirole (1.5 mg/kg) or saline each week for 7 weeks, during which time pouching behavior and body weight were monitored. Over the next 2 weeks, hamsters were tested for differences in prepulse inhibition of the acoustic startle response (PPI) and sexual behavior. Adenylate cyclase activation assays were then performed on dissected tissue from the nucleus accumbens and caudate-putamen. Results Repeated treatment with quinpirole increased pouching behavior and body weight and disrupted PPI. No changes in sexual activity in response to repeated quinpirole were found. Prior quinpirole treatment enhanced D-1 dopamine receptor-stimulated adenylate cyclase activity in the caudate-putamen that was blocked by co-incubation with the D-1 dopamine antagonist, SCH23390. Conclusions These results show that repeated activation of D-2-like receptors in vivo can produce changes in feeding behavior and sensory processing that is associated with sensitization of D-1 dopamine receptor-mediated signaling in the caudate-putamen.