Motivational properties of kappa and mu opioid receptor agonists studied with place and taste preference conditioning

Abstract

The reinforcing properties of various opioid agonists acting preferentially on the kappa and mu opioid receptors were assessed using taste and place preference conditioning procedures. Kappa receptor agonists produced conditioned aversions. Taste aversions were produced by all of the drugs used, including racemic mixtures of ethylketazocine, tifluadom, and U50-488, and active isomers (+)-tifluadom, (-)-bremazocine, and Mr 2034; corresponding inactive isomers either produced no effect of were less potent. Place aversions were produced by U50-488 and (-)-bremazocine, but not (+)-bremazocine or any of the other kappa receptor agonists tested with the taste procedure. The mu agonists produced predominantly conditioned preferences. Place preferences were produced by morphine, fentanyl and sufentanil. Taste preferences were produced by low doses of these substances; at higher doses the taste preferences were absent or replaced by aversions. Finally, with naloxone and lithium chloride it was shown that the taste procedure was more sensitive to punishing effects than the place procedure. It is concluded that kappa and mu opioid receptor agonists are effective unconditioned stimuli. From the lower portions of the dose response curves it is further concluded that activation of kappa opioid receptors has aversive properties and activation of mu receptors appetitive reinforcing properties. The findings are also discussed with regard to the prevailing notions of taste conditioning with opiates, and the reinforcing properties of activity of the endogenous opioid peptide systems.

Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats.

“…Nicotine stimulation of dopamine transmission is not due to a peripheral action since it was blocked by central but no peripheral nicotine antagonists. Drugs without rewarding properties (e.g., neuroleptics, tricyclic antidepressants, antimuscarinic drugs, and antihistamines) or with aversive properties [e.g., K opiate receptor agonists (17,18)] are devoid of the properties of the abused drugs outlined above. Thus, neuroleptics increase synaptic concentrations of dopamine in the accumbens but not in a preferential manner compared to the dorsal caudate.…”

AgRP(83–132) and SHU9119 differently affect activity-based anorexia

“…These data urge for further investigations on the involvement of other POMC-derived neuropeptides in the development of ABA, like B-endorphin. B-Endorphin stimulates food intake as well as rewarding processes and nociception (Amalric et al, 1987;Glass et al, 1999;Kalra and Horvath, 1998;Mucha and Herz, 1985;Przewlocki and Przewlocka, 2001). Yet a possible anorexic potency of B-endorphin was discovered by generating (male) B-endorphin-deficient mice, which are obese and hyperphagic (Appleyard et al, 2003).…”

κ-Opioid receptor modulation of accumbal dopamine concentration during operant ethanol self-administration

“…In contrast, activation of κ-opioid receptors (KOPr) within the mesolimbic circuitry decreases dopamine neuron firing (Margolis et al, 2003) and inhibits accumbal dopamine release (Heijna et al, 1990;Spanagel et al, 1992;Xi et al, 1998). Additionally, the administration of selective KOPr agonists causes conditioned-place aversions (Mucha and Herz, 1985;Bals-Kubik et al, 1993) and a suppression of drug self-administration (Lindholm et al, 2001;Mello and Negus, 1998;Xi et al, 1998).…”