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 D2-like dopamine receptor agonist, quinpirole, would produce neurochemical sensitization of D1 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 D1 dopamine receptor-stimulated adenylate cyclase activity in the caudate-putamen that was blocked by co-incubation with the D1 dopamine antagonist, SCH23390. Conclusions: These results show that repeated activation of D2-like receptors in vivo can produce changes in feeding behavior and sensory processing that is associated with sensitization of D1 dopamine receptor-mediated signaling in the caudate-putamen.
Bibliographical noteFunding Information:
Acknowledgments Supported by NIH grants DA 13680 (RLM) and MH60397 (VJW). We especially thank Melissa McCurley for her assistance with tissue collection. The experiments contained within this manuscript comply with the current laws of the USA.
- Dopamine receptor
- Prepulse inhibition
- Sexual behavior