ABSTRACT
RATIONALE: Exogenous brain-derived neurotrophic factor (BDNF) in the insular cortex (IC) is known to influence conditioned taste avoidance (CTA) learning, but little is known of its endogenous role in the phenomenon. Preexposure to many abusable compounds attenuates their ability to induce CTA, thus providing a possible platform from which to further elucidate the endogenous role of IC BDNF in CTA. OBJECTIVES: The role of IC BDNF in CTA learning was examined by assessing the effect of preexposure to methylphenidate (MPH) on MPH-induced CTA, followed by expression between preexposure groups of BDNF in the IC, central nucleus of the amygdala (CeA), and the nucleus accumbens (NAc). METHODS: Following preexposure to MPH (18 mg/kg), CTAs induced by MPH (0, 10, 18, and 32 mg/kg) were assessed in adult male Sprague-Dawley rats (n = 64). In separate groups (n = 31), differences in BDNF and tropomyosin-related kinase receptor-B (TrkB) were assessed using Western blots following similar preexposure and conditioning procedures. RESULTS: Preexposure to MPH significantly blunted MPH-CTA compared to preexposure to vehicle. Unexpectedly, there were no significant effects of MPH on BDNF activity following CTA, but animals preexposed to MPH exhibited decreased activity in the CeA and enhanced activity in the IC and NAc. CONCLUSIONS: Preexposure to MPH attenuates its aversive effects on subsequent presentations, and BDNF's impact on CTA learning may be dependent upon its temporal relation to other CTA-related intracellular cascades.
Subject(s)
Avoidance Learning/drug effects , Brain-Derived Neurotrophic Factor/metabolism , Cerebral Cortex/drug effects , Dopamine Uptake Inhibitors/pharmacology , Methylphenidate/pharmacology , Receptor, trkB/metabolism , Taste/drug effects , Amygdala/drug effects , Amygdala/metabolism , Animals , Cerebral Cortex/metabolism , Male , Nucleus Accumbens/drug effects , Nucleus Accumbens/metabolism , Phosphorylation , Rats , Rats, Sprague-Dawley , Signal Transduction/drug effects , Taste Perception/drug effectsABSTRACT
RATIONALE: Drug use and abuse is thought to be a function of the balance between its rewarding and aversive effects, such that the rewarding effects increase the likelihood of use while the drug's dissociable aversive effects limit it. Adolescents exhibit a shift in this balance toward reward, which may ultimately lead to increased use. Importantly, recent work shows that adolescents are also protected from the aversive effects of many abusable drugs as measured by conditioned taste avoidance (CTA). However, such effects of methylphenidate (MPH, widely prescribed to adolescents with ADHD) have not been characterized. OBJECTIVES: The effect of age on MPH-induced CTA was assessed. In addition, MPH-induced changes in brain-derived neurotrophic factor (BDNF) activity in the insular cortex (IC) and central nucleus of the amygdala (CeA), known to be important to CTA, were examined and related to CTAs in adolescents and adults. METHODS: CTAs induced by MPH (0, 10, 18, and 32 mg/kg) were assessed in adolescent (n = 34) and adult (n = 33) male Sprague Dawley rats. Following MPH CTA, IC and CeA tissue was probed for differences in BDNF and tropomyosin-related kinase receptor-B (TrkB) using Western blots. RESULTS: Blunted expression of MPH CTA was observed in the adolescents versus adults, which correlated with generally attenuated adolescent BDNF/TrkB activity in the IC, but the drug effects ran contrary to the expression of CTA. CONCLUSIONS: Adolescents are protected from the aversive effects of MPH versus adults, but further work is needed to characterize the possible involvement of BDNF/TrkB.
