Co-distribution of Fos- and mu opioid receptor immunoreactivity within therat septopreoptic area and hypothalamus during acute glucose deprivation: effects of the mu receptor antagonist CTOP

Mu (mu) opioid receptors occur throughout the brain, but central sites wher e ligand neuromodulatory effects occur during glucopenia have not been iden tified. The present studies investigated whether septal, preoptic, and hypo thalamic neurons that express immunoreactivity for this receptor are transc riptionally activated in response to the glucose antimetabolite, 2-deoxy-D- glucose (2DG), and if intracerebroventricular (icv) administration of the s elective mu receptor antagonist, CTOP, modifies this functional response to glucose substrate imbalance. Neurons labeled for mu receptor-immunoreactiv ity (-ir) were observed in the lateral septal nucleus (LS), medial septum ( MS), anterior division of the stria terminalis (BSTa), median preoptic nucl eus (MEPO), medial preoptic nucleus (MPN), parastrial nucleus (PS), anterio r hypothalamic periventricular nucleus (PVa), and lateral hypothalamic area (LPO). 2DG injection (400 mg/kg i.p.) resulted in co-labeling of mu recept or-positive neurons in the LS, MS, BSTa, MEPO, PVa, and LPO for nuclear Fos -ir. Icy delivery of CTOP decreased mean numbers of co-labeled neurons in t he LS, MS, BSTa, and MEPO. These results provide evidence for transactivati onal effects of glucopenia on mu opioid receptor-expressing neurons within the septum, preoptic area, and hypothalamus, and suggest that the functiona l status of these receptors within discrete septopreoptic sites may be crit ical for maximal glucoprivic induction of the Fos stimulus-transcription ca scade within local cells. These results thus support the view that the neur al loci described above may serve as substrates for regulatory effects of c t opioid receptor ligands on central compensatory activities during acute g lucose deprivation. (C) 2001 Elsevier Science Ireland Ltd. All rights reser ved.