• Rosa Maria Facciolo, Michele Crudo, Merylin Zizza, Giuseppina Giusi, and Marcello Canonaco.
• Comparative Neuroanatomy Laboratory, Ecology Department, University of Calabria, Arcavacata di Rende (CS), Italy. rm.facciolo@unical.it
• Neurotoxicol Teratol. 2011 Nov 1;33(6):641-50.

AbstractOrexins are one of the most potent orexigenic factors in fish that through their interaction with the GABA(A) receptor system assures the successful execution of feeding, motor and sleep-wake activities. In the present study, the effects of ORX-A (10ng/g BW) very greatly enhanced (p<0.001) the time spent in feeding behaviors while at the same time moderately increased (p<0.05) food intake of the goldfish. It is worthy to note that the great variations of time spent in feeding behaviors induced by β GABA(A)R agonist (muscimol, MUS) and antagonist (bicuculline, BIC) did not result to be correlated to any significant variations of food intake. It was, however, a T-maze study allowing us to establish that learning and mnemonic events very likely also operated in an ORX-A+GABA(A)R-dependent fashion in our fish model. Indeed, animals conditioned by red/blue lights greatly reduced latency time in the presence of ORX-A while neither MUS nor BIC alone modified such a parameter, with the exception of ORX-A+MUS being responsible for a moderate decrease of latency time with respect to conditioned fish treated with a saline solution. Conversely, ORX-A+MUS/BIC seemed to interfere with ORX-A actions as shown by their very great increase in latency time. Moreover, T-maze results appeared to be strengthened by evident ORXR transcriptional variations especially by the very great mRNA densities detected in some telencephalic regions of animals treated with ORX-A. Of all telencephalic regions Dl, considered homologous to the mammalian hippocampus, proved to be a major target for ORX-A effects. Overall, these data suggest that it is mainly the ORXergic system that promotes feeding behaviors via reward pathways in teleost fish as in mammals. Surprisingly, β GABA(A)R drugs did not modify such behaviors when given alone while the inhibitory effect on cognitive/reward processes was evoked when given together with ORX-A, suggesting that more than β subunits other GABA(A)R subunits could be promoting mnemonically guided motor behaviors.Copyright © 2011 Elsevier Inc. All rights reserved.

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