Chemogenetic activation of the perirhinal cortex reverses methamphetamine-induced memory deficits and reduces relapse
- 1Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA
- 2Department of Anesthesiology, Medical University of South Carolina, Charleston, South Carolina 29425, USA
- Corresponding author: reichel{at}musc.edu
Abstract
Prolonged use of methamphetamine (meth) has been associated with episodic memory deficits in humans, and preclinical rat models of meth self-administration indicate the memory deficits are a consequence of meth use. Others have suggested that the meth-induced memory deficits may promote a cyclical pattern of drug use, abstinence, and relapse, although preclinical evidence for this relationship is somewhat lacking. The memory deficits in preclinical models manifest as a loss of novel object recognition (NOR) memory. These deficits occur one to two weeks after cessation of meth use and involve the perirhinal cortex, a parahippocampal region essential to NOR memory. We hypothesized that a loss of perirhinal cortex function contributes to both the NOR memory deficits and increased vulnerability to relapse in a novel-cue reinstatement model. To test this, we attempted to restore NOR memory in meth rats using an excitatory Gq-DREADD in perirhinal neurons. Activation of these neurons not only reversed the meth-induced deficit in NOR memory, but also restored novelty salience in a novel-cue reinstatement model. Thus, perirhinal cortex functionality contributes to both memory deficits in relapse in a long-access model of meth self-administration in rats, and chemogenetic restoration of perirhinal function restores memory and reduces relapse.
Footnotes
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[Supplemental material is available for this article.]
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Article is online at http://www.learnmem.org/cgi/doi/10.1101/lm.046797.117.
- Received March 14, 2018.
- Accepted June 4, 2018.
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