Evidence that intermittent, excessive sugar intake causes endogenous opioid dependence.
OBJECTIVE
The goal was to determine whether withdrawal from sugar can cause signs of opioid dependence. Because palatable food stimulates neural systems that are implicated in drug addiction, it was hypothesized that intermittent, excessive sugar intake might create dependency, as indicated by withdrawal signs.


METHODS
Male rats were food-deprived for 12 hours daily, including 4 hours in the early dark, and then offered highly palatable 25% glucose in addition to chow for the next 12 hours. Withdrawal was induced by naloxone or food deprivation. Withdrawal signs were measured by observation, ultrasonic recordings, elevated plus maze tests, and in vivo microdialysis.


RESULTS
Naloxone (20 mg/kg intraperitoneally) caused somatic signs, such as teeth chattering, forepaw tremor, and head shakes. Food deprivation for 24 hours caused spontaneous withdrawal signs, such as teeth chattering. Naloxone (3 mg/kg subcutaneously) caused reduced time on the exposed arm of an elevated plus maze, where again significant teeth chattering was recorded. The plus maze anxiety effect was replicated with four control groups for comparison. Accumbens microdialysis revealed that naloxone (10 and 20 mg/kg intraperitoneally) decreased extracellular dopamine (DA), while dose-dependently increasing acetylcholine (ACh). The naloxone-induced DA/ACh imbalance was replicated with 10% sucrose and 3 mg/kg naloxone subcutaneously.


CONCLUSIONS
Repeated, excessive intake of sugar created a state in which an opioid antagonist caused behavioral and neurochemical signs of opioid withdrawal. The indices of anxiety and DA/ACh imbalance were qualitatively similar to withdrawal from morphine or nicotine, suggesting that the rats had become sugar-dependent.
Colantuoni
Carlo
C
Department of Psychology, Princeton University, New Jersey 08544, USA.
Rada
Pedro
P
McCarthy
Joseph
J
Patten
Caroline
C
Avena
Nicole M
NM
Chadeayne
Andrew
A
Hoebel
Bartley G
BG
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001007:Anxiety; D004032:Diet; D004040:Dietary Carbohydrates / Q000008:administration & dosage*; D004298:Dopamine / Q000378:metabolism; D005508:Food Deprivation; D005947:Glucose / Q000008:administration & dosage*; D007700:Kinetics; D008297:Male; D009270:Naloxone / Q000008:administration & dosage; D009714:Nucleus Accumbens / Q000378:metabolism; D018847:Opioid Peptides; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome; D019966:Substance-Related Disorders
D004040:Dietary Carbohydrates; D018847:Opioid Peptides; D009270:Naloxone; D005947:Glucose; D000109:Acetylcholine; D004298:Dopamine