Effects of self-administered methamphetamine on discrimination learning and reversal in nonhuman primates

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Abstract
Rationale Frequent exposure to methamphetamine has been reported to adversely influence cognitive behavior and, in particular, inhibitory control processes. Objective The present studies were conducted in squirrel monkeys to assess the effects of daily intravenous methamphetamine self-administration on touch screen-based repeated acquisition and discrimination reversal tasks thought to reflect behavioral dimensions of, respectively, learning and response inhibition. Methods First, stable methamphetamine-maintained behavior was established in each subject (0.35–1.6 mg/kg/session), and subsequently, a second daily session of discrimination learning was conducted (20 h later). Subjects first learned to discriminate between two simultaneously presented stimuli (acquisition) and, subsequently, to re-learn the discrimination with the contingencies switched (reversal). The role of the interval between self-administration and touch screen sessions was evaluated, as well as the effects of abrupt methamphetamine discontinuation. Results Results indicate that daily methamphetamine self-administration markedly disrupted the development of discrimination learning, initially requiring nearly twice the number of trials to master discriminations. The magnitude of adverse effects in individual subjects correlated to the level of daily methamphetamine intake. Importantly, however, behavioral disruption of discrimination learning was surmounted following remedial training. Once criterion levels of discrimination performance were achieved, subsequent development of reversal performance was largely unaffected except when the interval between self-administration and touch screen session was short and, thus, likely a result of methamphetamine’s direct effects. Discontinuation of methamphetamine produced no disruption in acquisition or reversal. Conclusion These results indicate that self-administered methamphetamine can markedly disrupt learning processes and highlight key differences in its effects on different aspects of discrimination learning.
Funding Information
  • National Institute on Drug Abuse (K01-DA035974, R01-DA035857)

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