Long-term blockade of mu-opioid receptors suggests a role in control of ingestive behaviour, body weight and core temperature in the rat.
Chronic subcutaneous infusion with a low dose (0.5 mg/kg/h) of naloxone via minipumps blocked the antinociceptive action of the mu-agonist, morphine, without affecting that of the kappa-agonist, U50488H. This dose resulted in a transient suppression in the rate of body weight gain and a sustained reduction in daily food intake (FI) and water intake (WI): this decrease was seen in both the light and dark phases. Naloxone also resulted in a reduction in resting core temperature (TC) in the light but not the dark phase. It did not affect the weight loss or hypothermia which accompanied 24 h food and water deprivation. Naloxone did, however, suppress FI and WI following deprivation and inhibited the recovery of body weight thereafter. The influence of naloxone upon FI, WI, TC and body weight was dose-dependent over 0.05-0.50 mg/kg/h. Increasing the dose to 3.0 mg/kg/h eliminated the antinociceptive action of U50,488H revealing a blockade of kappa- (in addition to mu-) receptors. This higher dose was not more effective in reducing FI, WI, body weight and TC than 0.5 mg/kg/h. Further, treatment with MR 2266, an antagonist (or weak partial agonist) with a higher activity at kappa-receptors than naloxone, was not more effective than naloxone in reducing FI, WI and body weight: further, it did not affect TC. Moreover, chronic infusion of bremazocine, (a kappa-agonist and mu-antagonist) reduced WI, FI, body weight and TC by a magnitude comparable to that of naloxone. Finally, chronic infusion of the mu-agonist, sufentanyl, led to a sustained rise in TC. It is concluded, that: (1) mu-opioid receptors may play a major role in the modulation of daily FI and WI and of body weight in freely behaving rats: this action is expressed in both the light and dark phases of the cycle and maintained following deprivation. The data provide no evidence for (but do not exclude) a particular role of kappa-receptors. (2) mu-Receptors play a physiological role in the modulation of TC in the light but not the dark phase of the daily cycle.
Millan
M J
MJ
Department of Neuropharmacology, Max-Planck-Institut für Psychiatrie, Planegg-Martinsried, F.R.G.
Morris
B J
BJ
D000818:Animals; D001575:Benzomorphans / Q000494:pharmacology; D001833:Body Temperature Regulation; D001835:Body Weight; D002940:Circadian Rhythm / Q000187:drug effects; D004327:Drinking Behavior / Q000187:drug effects / Q000502:physiology*; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D005283:Fentanyl / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017450:Receptors, Opioid, mu; D017409:Sufentanil
D001575:Benzomorphans; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D009270:Naloxone; C027247:MR 2266; D017409:Sufentanil; C027248:bremazocine; D005283:Fentanyl