The Effects of Chronic Psychostimulant Exposure on Morphine-Induced Antinociception and Tolerance
Widolff, Michelle Catherine Cyr
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Pre-weanling methylphenidate (MPH) exposure enhances systemic morphine-induced antinociception and tolerance in adult rats. This finding raises questions about the brain area(s) involved, the importance of developmental period during pretreatment, and whether other psychostimulants would produce similar effects. The purpose of the current studies was to address these unanswered questions. Four studies were conducted. Study 1 determined the potential involvement of the ventrolateral periaqueductal gray (vPAG) in MPH's long term enhancement of morphine-induced antinociception and tolerance. It appears that the vPAG is not exclusively involved, since the results observed in the previously mentioned systemic study were not replicated when morphine was microinjected into the vPAG. Study 2 helped determine methamphetamine (METH) doses for subsequent studies that were high enough to produce an acute behavioral effect similar to our MPH dose, but different from saline controls. Study 3 assessed the effects of chronic periadolescent MPH and METH exposure on adult morphine-induced antinociception and tolerance. Both age at pretreatment and psychostimulant compound used may mediate chronic MPH-induced enhancement of morphine-induced antinociception and tolerance, since all animals showed similar acute morphine-induced antinociception and only METH 3 mg/kg pretreated animals showed enhanced tolerance. Study 4 investigated whether morphine-induced antinociception and tolerance were altered following chronic adult exposure to MPH and METH. Different from pre-weanling and periadolescent animals, adult exposure to METH and MPH led to an acute reduction in morphine antinociceptive potency. In summary, the results demonstrate that (1) a brain area besides the vPAG must be involved in the enhancement of morphine-induced antinociception and tolerance observed following chronic pre-weanling MPH exposure, (2) the developmental period during which chronic psychostimulant exposure occurs impacts the degree and direction of effects on later morphine-induced antinociception and tolerance, and (3) different psychostimulant compounds may produce differing effects on morphine tolerance when exposure occurs during the periadolescent period of ontogeny.