Hypothalamic injection of non-opioid peptides increases gene expression of the opioid enkephalin in hypothalamic and mesolimbic nuclei: Possible mechanism underlying their behavioral effects.
The peptides galanin (GAL) and orexin (OX) share common features with the opioid enkephalin (ENK) in their relationship to ingestive behavior, stimulating consumption of a fat-rich diet and ethanol when injected into the hypothalamus. Since receptors for GAL and OX are dense in areas where ENK-expressing neurons are concentrated, these non-opioid peptides may exert their effects, in part, through the stimulation of endogenous ENK. This study was conducted to determine whether injection of GAL or OX affects the expression of ENK in hypothalamic and mesolimbic nuclei involved in consummatory behavior. Rats were injected with GAL (1 microg), OX-A (1 microg), or saline vehicle just dorsal to the hypothalamic paraventricular nucleus (PVN). They were sacrificed 1h later for analysis of ENK mRNA levels in the PVN, ventral tegmental area (VTA), central nucleus of the amygdala (CeA), and nucleus accumbens (NAc). Both GAL and OX had similar effects, significantly increasing ENK mRNA expression in each of these areas, except for the NAc. This enhanced ENK expression in the PVN, VTA and CeA was demonstrated with real-time quantitative polymerase chain reaction and confirmed in separate groups using radiolabeled and digoxigenin-labeled in situ hybridization. These findings demonstrate that the non-opioid peptides, GAL or OX, which have similar effects on consummatory behavior, are also similar in their effect on endogenous ENK. In light of published findings showing an opioid antagonist to block GAL- and OX-induced feeding, these results provide additional evidence that ENK is involved in mediating the common behavioral effects of these peptides.
The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. olga_karatayev@yahoo.com
Olga
O
Karatayev
Jessica R
JR
Barson
Guo-Qing
GQ
Chang
Sarah F
SF
Leibowitz
D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D004745:Enkephalins / Q000235:genetics*; D019004:Galanin / Q000008:administration & dosage / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D007031:Hypothalamus / Q000187:drug effects*; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009479:Neuropeptides / Q000008:administration & dosage / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D000068797:Orexins; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
D004745:Enkephalins; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D000068797:Orexins; D019004:Galanin