Differences in vulnerability and susceptibility to dexamphetamine in Nijmegen high and low responders to novelty: a dose-effect analysis of spatio-temporal programming of behaviour

Susceptibility to behavioural effects of dexamphetamine (0.5-2.0 mg/kg, SC) was analyzed in Nijmegen high responders to novelty (HR) and Nijmegen low responders to novelty (LR), using an automated ethological analysis. The main results were that, first, dexamphetamine was more toxic in HR than LR: 5.0 mg/kg dexamphetamine was lethal in 75% HR, respectively, 25% LR. Second, dexamphetamine had effects in HR at doses far lower than in LR: a dose of 0.5 or 1.0 mg/kg dexamphetamine was already sufficient to produce ceiling effects in HR, whereas a minimum dose of 2.0 mg/kg dexamphetamine was required to reach effects of a similar magnitude in LR. Third, the behavioural responses to 2.0 mg/kg dexamphetamine did not differ between HR and LR. These data show that HR are both more vulnerable and more susceptible to the toxic and behavioural effects of intermediate doses of dexamphetamine than LR. It is concluded that knowledge acquired previously about the neurochemical differences between Nijmegen HR (APO-SUS) and Nijmegen LR (APO-UNSUS) rats can be used to analyze further the mechanisms of action underlying individual-specific differences in drug abuse in animals and man.