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Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Effects of morphine on the plus-maze discriminative avoidance task: role of state-dependent learning
C L Patti1, S R Kameda, R C Carvalho
1Department of Pharmacology, Universidade Federal de São Paulo, Rua Botucatu, 862-Ed. Leal Prado, 04023-062 São Paulo, Brazil.
Rationale:
The amnesic effects of morphine may be related to its action on nociception, anxiety, or locomotion. This effect is also suggested to be related to state dependency.
Objectives:
The aims of this study were to verify the effects of morphine on mice tested in the plus-maze discriminative avoidance task (DAT) that uses light and noise as aversive stimuli and allows the concomitant evaluation of learning, memory, anxiety, and locomotion and also to verify the possible role of state-dependent learning in the effects of morphine.
Methods And Results:
The DAT was conducted in a modified elevated plus-maze. In the training, the aversive stimuli were applied when mice entered in one of the enclosed arms, whereas in the test, no stimuli were applied. The main results showed that (1) pretraining morphine (5-20 mg/kg i.p.) induced retrieval deficits (evaluated by the time spent in the aversive arm in the test) but not acquisition deficits (evaluated by the decrease in aversive arm exploration along the training); (2) pretest morphine (5-10 but not 20 mg/kg) counteracted this deficit; (3) morphine induced hypolocomotion (decreased number of entries in the arms), irrespective of memory alterations; and (4) morphine did not alter anxiety-like behavior (evaluated by the time spent in the open arms) during the training.
Conclusions:
Morphine given before training induces retrieval deficits in mice tested in the DAT, and these deficits could be related to morphine-induced state-dependent learning. Neither the memory deficit induced by pretraining morphine nor the reversal of this deficit by pretest morphine seems to be related to anxiety levels or locomotor alterations.
Insights
Morphine impairs memory retrieval in mice, potentially due to state-dependent learning. This memory deficit, induced by morphine before training, can be reversed by administering morphine before testing.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- Morphine's amnesic effects may involve nociception, anxiety, or locomotion.
- State-dependent learning is a potential factor in morphine-induced amnesia.
Purpose of the Study:
- To investigate morphine's effects on learning, memory, anxiety, and locomotion in mice using a plus-maze discriminative avoidance task (DAT).
- To explore the role of state-dependent learning in morphine's impact on memory.
Main Methods:
- Utilized a modified elevated plus-maze for the discriminative avoidance task (DAT) with light and noise as aversive stimuli.
- Administered morphine (5-20 mg/kg) before training or testing to assess acquisition, retrieval, anxiety, and locomotion.
Main Results:
- Pretraining morphine induced memory retrieval deficits but not acquisition deficits.
- Pretest morphine (5-10 mg/kg) reversed the retrieval deficits.
- Morphine caused hypolocomotion independently of memory effects.
- Morphine did not alter anxiety-like behavior during training.
Conclusions:
- Morphine administration before training causes retrieval deficits in the DAT, possibly linked to state-dependent learning.
- The memory deficits and their reversal by pretest morphine were not associated with anxiety or locomotion changes.
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