Opioid peptidergic systems modulate the activity of beta-adrenergic mechanisms during memory consolidation processes.
Post-training administration of the opioid receptor antagonist naloxone (0.1 mg/kg) facilitated 48-hr retention, in mice, of a one-trial step-through inhibitory avoidance response. The naloxone-induced memory facilitation was blocked in animals given the selective brain-noradrenergic neurotoxin DSP4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine) (50.0 mg/kg, ip) 7 days before training. Pretreatment with the norepinephrine-uptake inhibitor desmethylimipramine (10.0 mg/kg, ip, 30 min), but not with the serotonin-uptake inhibitor fluoxetine (5.0 mg/kg, ip, 30 min), prevented this antagonism. The simultaneous administration of the central beta-adrenoceptor blocker l-propranolol (2.0 mg/kg, ip), also blocked the effects of naloxone on memory. The effects of naloxone were not blocked by d-propranolol (2.0 mg/kg, ip), the peripheral beta-adrenoceptor blocker sotalol (2.0 mg/kg, ip), the alpha-adrenoceptor blocker phenoxybenzamine (10.0 mg/kg, ip), or the predominantly peripheral alpha-adrenoceptor blocker phentolamine (10.0 mg/kg, ip). These findings suggest that central beta-adrenergic mechanisms are involved in the effects of naloxone on memory. Naloxone (0.1 mg/kg, ip) potentiated the effects of the central beta-adrenoceptor agonist clenbuterol (0.001-1.00 mg/kg, ip), which, when administered alone, facilitates or impairs retention as a function of the dose injected. The simultaneous administration of beta-endorphin (0.1 micrograms/kg, ip) exerted effects opposite to those elicited by naloxone, that is, shifted the dose-response curve of clenbuterol to the right. Considered together, these findings are consistent with the view that the facilitatory action of naloxone on memory results from the release of central beta-adrenergic mechanisms from an inhibition induced by opioid peptides released during or immediately after training.
D000818:Animals; D002976:Clenbuterol / Q000008:administration & dosage; D004347:Drug Interactions; D004723:Endorphins / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012153:Retention, Psychology / Q000187:drug effects / Q000502:physiology*; D001615:beta-Endorphin
D004723:Endorphins; D011943:Receptors, Adrenergic, beta; D009270:Naloxone; D001615:beta-Endorphin; D002976:Clenbuterol