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Effects of the cannabinoid receptor 1 positive allosteric modulator GAT211 and acute MK-801 on visual attention and impulsivity in rats assessed using the five-choice serial reaction time task. | LitMetric

AI Article Synopsis

  • Altered interactions between endocannabinoid and glutamate signaling might play a role in schizophrenia and acute psychosis, highlighting the need for new treatments targeting these systems.
  • The study tested the effects of GAT211, a cannabinoid receptor 1 modulator, on cognitive function in rats with acute psychosis induced by MK-801, using tasks that measure attention and impulsivity.
  • Results showed that MK-801 significantly impaired attention and increased impulsivity in the rats, but GAT211 did not have any significant effects, suggesting further research is needed on cannabinoid modulators for cognitive symptoms in schizophrenia.

Article Abstract

Altered interactions between endocannabinoid and glutamate signaling may be involved in the pathophysiology of schizophrenia and acute psychosis. As cognitive disturbances are involved in schizophrenia, increased understanding of the roles of these neurotransmitter systems in cognition may lead to the development of novel therapeutics for disorder. In the present study, we examined the effects of a recently synthesized cannabinoid receptor 1 (CB1R) positive allosteric modulator GAT211 in a rodent model of acute psychosis induced by systemic treatment with MK-801. To assess cognitive function, we used the Five-Choice Serial Reaction Time (5CSRT) task, conducted in touchscreen-equipped operant conditioning chambers. Our measures of primary interest were accuracy - indicative of visual attentional capacity - and the number of premature responses - indicative of impulsivity. We also measured latencies, omissions, and perseverative responding during all test sessions. Thirteen adult male Long Evans rats were trained on the 5CSRT and were then tested using a repeated measures design with acute MK-801 (0 or 0.15 mg/kg, i.p.) and GAT211 (0, 3, or 10 mg/kg, i.p.) administration. Acute MK-801 severely impaired accuracy, increased omissions, and increased the number of premature responses. MK-801 also significantly increased correct response latencies, without significant effects on incorrect or reward correction latencies. GAT211 had no significant effects when administered alone, or in combination with acute MK-801. These data confirm the dramatic effects of acute MK-801 treatment on behavioral measures of attention and impulsivity. Continued investigation of CB1R positive allosteric modulators as potential treatments for the cognitive symptoms of schizophrenia and related disorders should be pursued in other rodent models.

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Source
http://dx.doi.org/10.1016/j.pnpbp.2020.110235DOI Listing

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