Effect of the GABAergic System on Memory Formation and State-Dependent Learning Induced by Morphine in Rats

Abstract

In the present study, the effects of intraperitoneal injections of GABA_A receptor agonist and antagonist on memory formation and morphine state-dependent learning were investigated in rats. Pre-training administration of morphine (1–15 mg/kg) in a step-down passive avoidance task induced state-dependent learning with impaired memory retrieval on the test day. The impairment of memory was restored after the pre-test administration of the same dose of morphine. The pre-test administration of the GABA_A receptor agonist, muscimol (0.01, 0.05 and 0.1 mg/kg), significantly decreased state-dependent retrieval induced by pre-test morphine (5 mg/kg). The state-dependency effect of morphine (1 mg/kg) was significantly potentiated by the pre-test administration of the GABA_A receptor antagonist, bicuculline (0.125, 0.25 and 0.5 mg/kg). Furthermore, the pre-training injection of muscimol (0.01 mg/kg) impaired memory retrieval which was restored by pre-test morphine (1, 3 and 5 mg/kg) administration. However, the pre-training administration of bicuculline did not affect retention by itself. In addition, amnesia induced by pre-training morphine (5 mg/kg) was significantly reversed in rats which had received pre-test injections of muscimol (0.01, 0.05 and 0.1 mg/kg). Pre-test injections of bicuculline (0.125, 0.25 and 0.5 mg/kg) significantly decreased morphine-induced amnesia. It is concluded that the GABA_A receptor mechanisms may be involved in the memory formation and it is postulated that these receptors may play an important role in morphine state-dependent learning.

Role of the central amygdala GABA-A receptors in morphine state-dependent memory

“…This may be in agreement with our previous report that systemic administration of muscimol inhibited the similar morphine response (Zarrindast et al 2006b). GABA and opioid receptors exert interactions in different ways.…”

Involvement of a Dysfunctional Dopamine-D1/N-Methyl-d-aspartate-NR1 and Ca2+/Calmodulin-Dependent Protein Kinase II Pathway in the Impairment of Latent Learning in a Model of Schizophrenia Induced by Phencyclidine

“…4A). State-dependent learning denotes the fact that information that has been learned while an animal is under the influence of a certain drug (state) can only be recalled when the animal is in the same state in which the information was learned, not in a different (i.e., undrugged) state (Zarrindast et al, 2006). The mice infused with 10 nmol of KN93 before both the training and test trials showed a significantly prolonged finding latency in the test trial compared with the mice treated with vehicle (data not shown).…”

Neurobiology of Memory and Anxiety: From Genes to Behavior

“…Moreover, various GABA analogs and agents affecting transmitter metabolism to enhance GABAergic tone have been reported to exert anxiolytic effects [98, 102–107]. The role of GABA in learning and memory has also been widely recognized [28–30, 90, 100, 108–112]. Three comprehensive reviews particularly [12, 17, 113] emphasize the role of central GABA in memory-anxiety interplay, noting amnestic/anxiolytic effects of positive, and opposite profiles of negative, GABA modulators (also see [27–30, 111, 114, 115] for details).…”