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Stimulation and antagonism of opioid delta-receptors produce opposite effects on active avoidance conditioning in
G Schulteis1, J L Martinez, V J Hruby
1Department of Psychology, University of California, Berkeley 94720.
Abstract:
The effects of opioid delta-receptor activation on conditioning in a one-way active avoidance paradigm were investigated in mice. Peripheral administration of 30 and 100 micrograms/kg of [Leu5]enkephalin (LE) and 11.6 micrograms/kg of [D-Pen2,D-Pen5]enkephalin (DPDPE), a synthetic enkephalin analog with high delta-selectivity, impaired acquisition of avoidance responding. The dose response functions for both peptides were U-shaped. Deficits in responding were also present 24 hours after training, which suggests that the impaired performance observed during training was not an impairment in the ability of the mice to perform. Also, neither LE nor DPDPE decreased footshock sensitivity or open-field activity, which rules out analgesia and decreased activity levels as likely explanations for the deficits in conditioning. Finally, antagonizing endogenous ligands with the delta-selective antagonist ICI 154,129 enhanced acquisition, an effect opposite that produced by LE and DPDPE. The results suggest that activation of delta-receptors is normally involved in the modulation of active avoidance learning.
Insights
Opioid delta-receptor activation impairs active avoidance learning in mice. Blocking these receptors enhances learning, suggesting their normal role in modulating this behavior.
Area of Science:
- Neuroscience
- Behavioral Neuroscience
- Pharmacology
Background:
- Opioid receptors play a role in learning and memory.
- Delta-opioid receptors are implicated in various behavioral processes.
Purpose of the Study:
- To investigate the role of delta-opioid receptor activation in active avoidance learning.
- To determine if peripheral administration of delta-opioid receptor agonists affects conditioning.
Main Methods:
- Mice were trained in a one-way active avoidance paradigm.
- Administration of [Leu5]enkephalin (LE) and [D-Pen2,D-Pen5]enkephalin (DPDPE) at specific doses.
- Assessment of footshock sensitivity and open-field activity.
- Administration of a delta-selective antagonist (ICI 154,129).
Main Results:
- Both LE and DPDPE impaired the acquisition of avoidance responding in a U-shaped dose-dependent manner.
- Performance deficits persisted 24 hours post-training, indicating an effect on learning, not motor ability.
- Neither agonist affected footshock sensitivity or open-field activity, ruling out analgesia or sedation.
- The delta-selective antagonist ICI 154,129 enhanced avoidance learning, opposing the agonist effects.
Conclusions:
- Activation of delta-opioid receptors negatively modulates active avoidance learning.
- Endogenous delta-opioid receptor ligands may play a role in regulating this learning process.
- Delta-opioid receptors are potential targets for interventions related to learning and memory.