Alpha GABAA subunit-orexin receptor interactions activate learning/motivational pathways in the goldfish

Orexins (ORXs) cross-talking with gamma-aminobutyric acidA receptor (GABAAR) is beginning to constitute akey neuronal signaling feature responsible for the successful promotion of sleep–wake cycle, feeding andmotor behaviors plus reward/motivational activities. In this work, ORX-A and the two alpha GABAAR agonists(zolpidem, ZOL; diazepam, DZP) accounted for very great (p < 0.001) increases of feeding while only DZPelicited great (p < 0.01) levels of food intake in the goldfish (Carassius auratus). It was, however, T-maze andconditioned place preference (CPP) methods that allowed us to specifically establish learning/rewardrelatedevents operating in an ORX-A + GABAAR-dependent fashion in our experimental model. T-mazedata showed that conditioned ORX-A treated-fish were capable of reaching the red/blue chamber andingesting their food reward in a very greatly reduced latency time with respect to untreated conditionedfish while DZP and ZOL greatly and moderately (p < 0.05) reduced their latency time, respectively. RegardingCPP study, conditioned ORX-A- and DZP-treated animals showed comparably greater preferences forthe conditioned compartment that became even greater in ORX-A + DZP-treated fish. Surprisingly, ORXreceptor expression of the telencephalon was preferentially activated by ORX-A treatments while diencephalic/mesencephalic structures and namely the tuberculum posterioris (TPp) were more sensitive toDZP especially following treatment with ORX-A + DZP. Overall, behavioral performances along with ORXreceptor transcriptional properties tend to point to GABAAR agonists as enhancers of palatability whilethe ORXergic system constitutes a crucial link between satiety-related and cognitive centers through theactivation of TPp thus proposing this ascending dopaminergic system as a key target of learning/rewardprocesses in fish.