Differential effects of intrahypothalamic administration of opioids on food intake in naive and tolerant rats.

We investigated the effects of intrahypothalamic administrations of the opioid agonists morphine (MOR) and ketocyclazocine (KCZ) and antagonists naltrexone (NALTX) and Mr2266 on food intake (FI) during light and dark phases of the diurnal cycle, after acute or chronic administration in rats. Acute intralateral hypothalamic (LH) administration of MOR or KCZ (1 microgram/rat) enhanced FI during dark and light phases, respectively, whereas intraventromedial hypothalamic (VMH) injections resulted in moderate hyperphagia during dark phases by both mu and kappa agonists. The receptor specificity was evident from blockade of the responses to MOR or KCZ by the respective antagonists NALTX and Mr2266. After repeated administrations of MOR and KCZ, FI responses to the test dose of these agonists injected in LH were modulated in opposite directions. However, the adaptative changes in FI after intra-VMH injection of KCZ were similar to those seen with MOR. These results are discussed in light of a differential opioid receptor involvement and their possible functional interactions within the hypothalamus during food intake.