The effects of chronic naltrexone treatment on lateral hypothalamic self-stimulation, stimulation-escape, and stimulation-induced feeding
This work investigates the role of endogenous opioids in three behaviors induced by lateral hypothalamic (LH) stimulation: reward, escape and feeding.
Studies addressing the issue of whether LH stimulation reward is mediated by endogenous opioids have thus far failed to produce conclusive results. These studies, using the broad-spectrum opioid receptor antagonists naloxone (NAL) and naltrexone (NTX), have invariably suffered from high between-subjects variability. We report a set of experiments that elucidate the nature of this variability using opioid receptor unregulation and supersensitivity to endogenous opioid peptides induced by chronic NTX treatment.
Results indicate that electrode placement within the LH, a previously uncontrolled variable, determines the extent to which LH self-stimulation (SS) is mediated by opioid mechanisms. Following chronic NTX treatment, SS is potentiated only at electrode placements that do not support stimulation-escape (SE); these placements lie caudally within the LH. At rostrally located electrodes that do support SE, neither SS nor SE are altered. An ancillary experiment using acute NTX showed a similar dependence of NTX effects on electrode placement and suggested the presence of an opioid mechanism inhibitory to reward. This mechanism appears to be activated only by stimulation at mid-hypothalamic (tuberal) levels.
Past studies have shown that LH stimulation-induced feeding (SIF) is clearly mediated by endogenous opioids since it is inhibited by systematically applied NAL and NTX, and facilitated by systematically applied opioid agonists. However, consequent to chronic NTX treatment, we observed an increase in SIF thresholds relative to baseline levels. It is proposed that this response is effected at the periaqueductal gray or peripherally, since opioid agonists acting locally within these regions disrupt LH SIF. Our findings suggest that there exists an opioid mechanism that is inhibitory to feeding.