Effects of Methamphetamine Exposure on Fear Learning and Memory in Adult and Adolescent Rats
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Methamphetamine (meth) use is often comorbid with anxiety disorders, with both conditions predominant during adolescence. Conditioned fear extinction is the most widely used model to study the fear learning and regulation that are relevant for anxiety disorders. The present study investigates how meth binge injections or meth self-administration affect subsequent fear conditioning, extinction and retrieval in adult and adolescent rats. In experiment 1, postnatal day 35 (P35—adolescent) and P70 (adult) rats were intraperitoneally injected with increasing doses of meth across 9 days. At P50 or P85, they underwent fear conditioning followed by extinction and test. In experiments 2a–c, P35 or P70 rats self-administered meth for 11 days then received fear conditioning at P50 or P85, followed by extinction and test. We observed that meth binge exposure caused a significant disruption of extinction retrieval in adult but not adolescent rats. Interestingly, meth self-administration in adolescence or adulthood disrupted acquisition of conditioned freezing in adulthood. Meth self-administration in adolescence did not affect conditioned freezing in adolescence. These results suggest that intraperitoneal injections of high doses of meth and meth self-administration have dissociated effects on fear conditioning and extinction during adulthood, while adolescent fear conditioning and extinction are unaffected.
KeywordsMethamphetamine Self-administration Fear Extinction Rats Adolescence
This research was supported by funding from National Health and Medical Research Council (NHMRC)/Australian Research Council (ARC) Fellowship (CJP); NHMRC Career Development Fellowship (JHK), NHMRC Principal Research Fellowship (AJL), Brain Behavior Research Foundation (JHK) and the Victorian State Government Operational Infrastructure Scheme.
Compliance with Ethical Standards
Conflict of interest
All authors declare that they have no conflict of interest.
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