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Interaction between catecholaminergic and opioid systems in an active avoidance task
1Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
Abstract:
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.
Insights
Naloxone impaired learning in mice, but its effects on memory depended on prior DSP4 treatment, suggesting state-dependent modulation. DSP4 alone impaired learning but not memory recall.
Area of Science:
- Neuroscience
- Behavioral Pharmacology
Background:
- Noradrenergic pathways are crucial for learning and memory.
- DSP4 is a neurotoxin that selectively depletes noradrenaline.
- Naloxone is an opioid antagonist with potential effects on learning and memory.
Purpose of the Study:
- To investigate the effects of DSP4 pretreatment on naloxone's modulation of active avoidance learning and memory.
- To explore potential state-dependent effects of naloxone in noradrenergic-depleted mice.
Main Methods:
- Male NMRI mice were pretreated with DSP4 or vehicle.
- Animals underwent a two-day active avoidance task training.
- Naloxone was administered at different doses before training sessions.
Main Results:
- Naloxone dose-dependently impaired acquisition in vehicle-pretreated mice.
- Naloxone differentially affected retention in vehicle-pretreated mice (1 mg/kg facilitated, 10 mg/kg impaired).
- DSP4 alone impaired acquisition but not retention.
- Naloxone's effects on acquisition and retention were altered in DSP4-pretreated mice, suggesting state-dependent modulation.
Conclusions:
- DSP4 pretreatment alters naloxone's effects on active avoidance learning and memory.
- Results support a role for state-dependent processes in naloxone's action in noradrenergic-depleted animals.
- Further research is needed to elucidate the mechanisms underlying these state-dependent effects.