Intra-striatum lodoxamide produced conditioning place preference in rats via GPR35 independent mechanisms

The function of the protein-coupled receptor 35 (GPR35) in the central nervous system (CNS) remains largely unknown. Due to its expression in the ventral striatum, a key area in the brain reward system, the function of GPR35 in reinforcing actions is questioning. To analyze if activation of GPR35 in the ventral striatum is related to reinforcing actions, male Wistar rats (250-300 g) received stereotaxic surgery from placing guide cannulae in the ventral striatum. Different doses of lodoxamide (a full rat-GPR35 agonist) or vehicle (DMSO 10%) were injected (intra-ventral-striatum) in the absence and during the pretreatment with ML-194 (a selective GPR35 antagonist). Lodoxamide (100 pmol) induced a significant increment in preference for the drug-conditioning chamber (p < 0.05), but not vehicle or ML-194 per se (p > 0.05). On the other hand, the pretreatment with ML-194 did not prevent lodoxamide's reinforcing effects. Thus, the reinforcing actions of lodoxamide (intra-ventral-striatum) involve mechanisms likely independent of GPR35.