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Dual effect of morphine in long-term social memory in rat
Enrica Bianchi1, Cristina Menicacci, Carla Ghelardini
1Department of Medical Surgical Sciences and Neuroscience, University of Siena, Siena, Italy. enrica.bianchi@unisi.it
Background And Purpose:
Bimodal dose-response relationships have been demonstrated in animals and humans following morphine administration. We examined if systemic administration of morphine, in extremely low (μg) and high (mg, analgesic) doses, changed the learning process.
Experimental Approach:
In the social learning test, an adult rat investigates a juvenile. The juvenile is submitted to a second encounter after a few days and investigation by the adult should be reduced. Morphine was administered before the first encounter between rats, and the critical test was performed 24, 72 or 168 h later, when animals were re-exposed to each other, in the absence of morphine.
Key Results:
Low doses of morphine, comparable with endogenous brain concentrations, enhanced long-term memory recognition; while high doses did the reverse, indicating the adult failed to recognize the juvenile. Recognition of a familiar rat appeared to be mediated within the brain accessory olfactory bulb (AOB) by an opioid system intrinsic to the olfactory system through μ-opioid receptors (MORs). At this supraspinal site, the PLC/PKC signalling pathway was activated by extremely low morphine doses.
Conclusions And Implications:
Morphine treatment administration may either disrupt or facilitate social memory, depending on the dose, extending to memory formation the bimodal effects of morphine previously shown in pain. Social memory formation elicited by extremely low morphine doses, was mediated within the AOB by an opioid system, intrinsic to the olfactory system through MORs.
Insights
Extremely low doses of morphine enhance social memory in rats, while high doses impair it. This suggests morphine
Area of Science:
- Neuroscience
- Pharmacology
- Animal Behavior
Background:
- Bimodal dose-response relationships for morphine are known in humans and animals.
- Morphine's effects on learning and memory require further investigation.
Purpose of the Study:
- To investigate the impact of extremely low (μg) and high (mg) doses of morphine on social learning and memory in rats.
- To elucidate the neural mechanisms underlying morphine's dose-dependent effects on social recognition.
Main Methods:
- A social learning test involving adult and juvenile rats was employed.
- Morphine was administered before initial social interaction, with memory tested at 24, 72, and 168 hours post-administration.
Main Results:
- Low-dose morphine enhanced long-term social memory recognition.
- High-dose morphine impaired social recognition, indicating a failure to recognize familiar individuals.
- Recognition was mediated in the accessory olfactory bulb (AOB) via μ-opioid receptors (MORs) and the PLC/PKC pathway.
Conclusions:
- Morphine administration exhibits dose-dependent effects on social memory, either facilitating or disrupting it.
- Extremely low doses of morphine enhance social memory through an opioid system within the olfactory system's AOB.
- These findings extend the known bimodal effects of morphine from pain to memory formation.
