Abstract
In state-dependency, information retrieval is most efficient when the animal is in the same state as it was during the information acquisition. State-dependency has been implicated in a variety of learning and memory processes, but its mechanisms remain to be resolved. Here, mice deficient in AMPA-type glutamate receptor GluA1 subunits were first conditioned to morphine (10 or 20 mg/kg s.c. during eight sessions over four days) using an unbiased procedure, followed by testing for conditioned place preference at morphine states that were the same as or different from the one the mice were conditioned to. In GluA1 wildtype littermate mice the same-state morphine dose produced the greatest expression of place preference, while in the knockout mice no place preference was then detected. Both wildtype and knockout mice expressed moderate morphine-induced place preference when not at the morphine state (saline treatment at the test); in this case, place preference was weaker than that in the same-state test in wildtype mice. No correlation between place preference scores and locomotor activity during testing was found. Additionally, as compared to the controls, the knockout mice showed unchanged sensitization to morphine, morphine drug discrimination and brain regional μ-opioid receptor signal transduction at the G-protein level. However, the knockout mice failed to show increased AMPA/NMDA receptor current ratios in the ventral tegmental area dopamine neurons of midbrain slices after a single injection of morphine (10 mg/kg, s.c., sliced prepared 24 h afterwards), in contrast to the wildtype mice. The results indicate impaired drug-induced state-dependency in GluA1 knockout mice, correlating with impaired opioid-induced glutamate receptor neuroplasticity.
Highlights
In state-dependency, information retrieval is most efficient when the animal is in the same state as it was during the information acquisition
No habituation was seen in GluA1+/+ mice, with their locomotor activity remaining constant throughout the saline trials
We found that morphine state-dependency was altered in the mouse line lacking the GluA1 subunit of the amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor
Summary
In state-dependency, information retrieval is most efficient when the animal is in the same state as it was during the information acquisition. Drugs induce an internal state (an affect) that can act as a cue in learning process: when an animal learns a behavior while intoxicated, it later better recalls the behavior while being again intoxicated. Glutamate receptors of a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type (for review, see [8]) possess a dual role in neuronal communication. They are mediators of fastacting excitatory neurotransmission, and second, changes in their regulation constitute a molecular mechanism of neuronal adaptation underlying long-term potentiation, a putative cellular correlate of learning and memory [9]. AMPA receptor GluA1 subunit-deficient mouse line (GluA12/2 mice) shows adaptation-dependent defects at neuronal circuitry [10] and behavioral [11] levels, suggesting that GluA1 subunit has a major role in neuronal adaptation
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