Previous studies have demonstrated that several antipsychotic drugs can produce body weight gain through an inhibition of the sympathetic effects of orexin.

The aim of the present work was to study the possible involvement of AMPKa in the effects of orexin and of the typical antipsychotic drug haloperidol.

18 male rats were divided in four groups; rats were alternatively treated with an i.c.v. injection of Orexin A (group 1), an i.c.v. injection of saline (group 2), an i.p. injection of haloperidol (group 3) or an i.p. injection of saline (group 4). All rats were sacrificed two hours after the injection and AMPKa and pAMPKa in the hyphotalamus were analyzed by Western blot along with the immunohistochemical analysis of pAMPKa.

The results showed an increase in pAMPKa expression after the icv injection of orexin compared to the control, and a decrease in pAMPKa after the treatment with haloperidol compared to the control. No modification of AMPK was seen between any group. The immunohistochemistry showed a decrease of pAMPKa in the lateral and ventromedial nucleus of the hyphotalamus after the haloperidol injection.

These data demonstrate that orexin alters the AMPK activity in the hyphotalamus suggesting a possible role of AMPK in the orexinergic effect of orexin. Moreover it can be argued that the effect of haloperidol on AMPK is mediated by the orexinergic system.