Abstract
Studies have shown that inflammation and neurodegeneration may accompany the development of addiction to apomorphine and that the glutamate NMDA receptor antagonist, memantine, may be neuroprotective. The similarity between apomorphine and dopamine with regard to their chemical, pharmacological and toxicological properties provided a basis for investigating the mechanism of action of the former agent. In this study, we investigated whether memantine would suppress apomorphine-seeking behavior in rats subjected to apomorphine-induced place preference conditioning, through modulation of NMDA receptors in the prefrontal cortex. Repeated apomorphine (1 mg/kg) treatment induced conditioned place preference (CPP) and had no significant effect on NMDA receptor levels in the prefrontal cortex. Prior treatment with memantine (5 mg/kg or 10 mg/kg) increased the levels of NMDA receptors in the prefrontal cortex but did not suppress CPP induced by apomorphine. These data give further support to the addictive effect of apomorphine and demonstrate that blockade of NMDA receptors by memantine is unable to suppress apomorphine-seeking behavior.
Highlights
The risk of development of addictive behavior as a side effect of many pharmacological therapies for psychiatric disorders, has increased in the last two decades and represents a serious problem in our societies today [1]
We investigated whether memantine would suppress apomorphine-seeking behavior in rats subjected to apomorphine-induced place preference conditioning, through modulation of NMDA receptors in the prefrontal cortex
The Bonferroni test for differences between time spent in the apomorphine-associated compartment during the pre-treatment and post-treatment sessions showed no significant differences in saline (Sal) and memantine 5 mg (Mem5) treated groups (p > 0.05)
Summary
The risk of development of addictive behavior as a side effect of many pharmacological therapies for psychiatric disorders, has increased in the last two decades and represents a serious problem in our societies today [1] Among these drugs is apomorphine, a non-narcotic derivate of morphine, which acts as a dopamine receptor agonist to produce psychostimulant-like effects [2]. Morphological studies support the existence of axon-axon synapses of glutamate and dopamine neurons in the medial PFC, ventral striatum and NAcc providing evidence at the synaptic level for interactions between these two neurotransmitters [13] These findings provide both an anatomical and functional basis for a role for glutamate in addiction and support initiatives that investigate its contribution to the development of substance use disorders. We focussed on this brain region as it appears to be central to the effects of both dopamine and glutamate in their regulation of emotional responses, cognitive control, and executive functions [17]
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