α GABA(A) subunit-orexin receptor interactions activate learning/motivational pathways in the goldfish

Abstract

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