Glycyl-glutamine reduces ethanol intake at three reward sites in P rats.
beta-endorphin, implicated in modulation of ethyl alcohol reward, has neuron terminals in several reward sites. Alcohol consumption was reduced after ventricular or site-specific injections into the nucleus accumbens of an opioid-derived dipeptide, glycyl-glutamine. The current study examined the effects of this dipeptide after site-specific injections into additional reward sites. Alcohol-preferring (P) rats, stereotaxically implanted with bilateral guide cannulae into the nucleus accumbens, ventral tegmental area, and the central nucleus of the amygdala were given 30% alcohol and water in a 24h voluntary two-bottle choice paradigm. Upon achieving stable baseline intakes, glycyl-glutamine (GQ) doses were injected bilaterally, and the alcohol and water intakes and body weight recorded for the response and recovery. The data show reduced alcohol intake by 32-49.5% after 100-pmol glycyl-glutamine into reward sites (nucleus accumbens, ventral tegmental area, and central nucleus of the amygdala), but not after injections into control sites dorsal to reward sites. The order of sensitivity to the 1-fmol dose was amygdala > or = ventral tegmental area > accumbens. GQ was effective in reducing ethanol intake at reported beta-endorphin terminal regions in each of the three reward sites tested. The effective doses were similar to reported endogenous GQ levels, consistent with the notion that it may function as part of an endogenous counter regulatory mechanism and represent a "stop drinking" signal in the high drinking, P rats at these three reward sites.
Resch
Garth E
GE
School of Biological Sciences, Division of Molecular Biology and Biochemistry, University of Missouri at Kansas City, Kansas City, MO 64110, USA. reschg@umkc.edu
Simpson
C Wayne
CW
D000428:Alcohol Drinking / Q000188:drug therapy*; D000679:Amygdala / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D004151:Dipeptides / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology; D051381:Rats; D012201:Reward; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology; D001615:beta-Endorphin / Q000502:physiology
D004151:Dipeptides; C039788:glycylglutamine; D001615:beta-Endorphin