Diet-induced Enhancement Of Naloxone Sensitivity Is Independent Of Changes In Body Weight.

Intake of palatable solutions can enhance the anorectic potency of opioid antagonists. This experiment examined the relative contributions of orosensory experience and body weight gain to the enhanced anorectic potency of naloxone (0.125, 0.25, 0.5, and 1.0 mg/kg i.p.). Four groups of male hooded Lister rats (Charles River) were maintained on separate feeding regimes for 3 months. S-ADLIB rats were nondeprived with free access to lab chow and 20% (w/v) sucrose solution. S-RESTRICT rats received limited sucrose (50 ml/day) and chow (15 g/day) access, yoking their body weights to ADLIB rats receiving free access to lab chow only. RESTRICT rats received approx. 15 g of chow/day to maintain their body weights at 90% of the ADLIB rats. Fifteen-minute sucrose intake tests revealed marked differences between naloxone sensitivity of chronic sucrose drinkers and sucrose-naive groups. Intakes of S-ADLIB and S-RESTRICT were suppressed at all doses (max suppression >60%). In comparison to animals given sucrose, ADLIB and RESTRICT animals were significantly less sensitive (maximum suppression = 35%). Naloxone potency was independent of body weight differences. The data demonstrate that overconsumption of palatable ingesta, and not diet-induced weight gain, is sufficient to enhance antagonist potency. The study confirms that orosensory stimulation can induce plasticity in opioid systems, supporting an important role for opioids in intake regulation and general reward processes.