REPEATED ADMINISTRATION OF AMPHETAMINE INDUCES SENSITIZATION TO ITS DISRUPTIVE EFFECT ON PREPULSE INHIBITION IN THE RAT

Male Sprague-Dawley rats were repeatedly treated with amphetamine (AMP , 1 mg/kg, SC) at 3-day intervals for 15 days and tested for prepulse inhibition of acoustic startle after each treatment. This treatment re gimen induced sensitisation in the animals as evidenced by a progressi ve increase in the disruptive effect of AMP on prepulse inhibition. Pe rsistent changes in brain function was indicated, since an increase in disruptive effect was observed in sensitised animals also after a 22- day-long drug-and test-free period. The development of sensitisation w as blocked by pretreatment with haloperidol (HPD, 0.1 mg/kg, SC), whic h suggests that sensitisation to the disruptive effect of AMP was depe ndent on dopamine (DA) D-2 receptor activation. Furthermore, the devel opment of sensitisation was blocked by adrenalectomy, which suggests t hat sensitisation was dependent also on circulating adrenal hormones. Increased DA-ergic activity has been implicated in the pathophysiology of schizophrenia and AMP-induced sensitisation to the neuronal functi ons that modulate prepulse inhibition may be an experimental model to investigate this hypothesis.