Interaction between catecholaminergic and opioid systems in an active avoidance task.
Male NMRI mice were given intravenous injections of the noradrenergic neurotoxin DSP4 or the vehicle 24 to 72 h prior behavioral testing. Animals were given 2 days of training on a one-way active avoidance task. Naloxone was given in one of three doses prior to training on Day 1 and Day 2 or prior to training on Day 1 only (saline was given prior to training on Day 2). There was a dose-dependent impairment of acquisition by naloxone in the vehicle-pretreated groups; 10 mg/kg naloxone produced a significant impairment of acquisition. Naloxone also modulated retention (Day 2) performance of the active avoidance task. For vehicle-pretreated mice, 1 mg/kg naloxone facilitated and 10 mg/kg naloxone-impaired performance on Day 2. DSP4 alone produced an impairment of acquisition of this task but had no effect on retention; Day 2 scores were slightly higher in the DSP4-pretreated group than in the vehicle-pretreated group. Naloxone produced somewhat different effects in DSP4-pretreated animals than in vehicle-pretreated animals. Naloxone (1 mg/kg) ameliorated the DSP4-induced impairment of acquisition; 10 mg/kg naloxone did not significantly alter the acquisition performance of this group. For the DSP4-pretreated mice that received naloxone before training on both days, the dose-response characteristics for retention scores were similar to those of vehicle-pretreated mice; 1 mg/kg naloxone was the facilitatory dose. However, for DSP4-treated mice that received naloxone before training on Day 1 only, there was a shift to the right in the effective facilitatory dose of naloxone. For these animals, 10 mg/kg naloxone but not 1 mg/kg naloxone significantly enhanced retention performance. We discuss these results in the context of a possible state-dependent modulation by naloxone in the DSP4-treated animals.
Bennett
M C
MC
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
Hock
F J
FJ
D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D001596:Benzylamines / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004723:Endorphins / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology*; D011939:Mental Recall / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D009270:Naloxone / Q000494:pharmacology; D009498:Neurotoxins / Q000494:pharmacology; D009638:Norepinephrine / Q000502:physiology*; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000502:physiology*; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D012153:Retention, Psychology / Q000502:physiology
D001596:Benzylamines; D004723:Endorphins; D009498:Neurotoxins; D011941:Receptors, Adrenergic; D011957:Receptors, Opioid; D009270:Naloxone; C012102:DSP 4; D009638:Norepinephrine