Different behavioral effects of daily or intermittent dexamphetamine administration in Nijmegen high and low responders

Outbred strains of Wistar rats contain both high responders to novelty (HR) and low responders to novelty (LR). Male HR and LR selected from the Nijmegen outbred strain of Wistar rats differ in their sensitivity to acute administration of dexamphetamine (AMPH). Sub-chronic administration of AMPH sensitizes rats to this agent, and this sensitization (SENS) increases when an intermittent, instead of continuous, regimen is used. Thus, the question arose whether HR and LR also differ in the development of sensitization to AMPH. AMPH (0.5 mg/kg SC) was given five times either each consecutive day (daily: DAY) or each alternate day (intermittent: INT). Drug-induced changes in the spatio-temporal patterning of open field behavior were assessed for a period of 45 min. Three sets of data were found: i) in the AMPH-DAY conditions: total number of excursions with 0 stops increased in time; this SENS was far greater in HR than in LR; ii) the effects under AMPH-DAY conditions were far greater that those under AMPH-INT conditions, especially in HR; iii) under AMPH-INT conditions a new phenomenon was observed: following a period in which SENS occurred, a period marked by desensitization appeared which, in turn, was followed by a period with SENS being greater than the SENS seen during the first time, this effect was far more pronounced in HR than in LR. It is concluded that AMPH-INT induces time-dependent changes marked by consecutive periods of SENS and desensitization. This has far-reaching consequences for hypotheses about processes giving rise to the development of (1) SENS to psychostimulants and, consequently, (2) certain aspects of addiction to these drugs.