EVIDENCE FOR DISSOCIABLE MECHANISMS OF AMPHETAMINE-INDUCED AND STRESS-INDUCED BEHAVIORAL SENSITIZATION - EFFECTS OF MK-801 AND HALOPERIDOL PRETREATMENT

The present study examined the ability of pretreatment with MK-801 or haloperidol to block the induction of behavioral sensitization to amph etamine challenge by repeated immobilization stress in male Sprague-Da wley rats. Fifteen minutes before each of ten 30-min restraint session s, rats were administered saline, MK-801 (0.01, 0.10 or 0.25 mg/kg IP) or haloperidol (0.10 or 0.25 mg/kg IF). Control rats received the sam e injection regimen without restraint. An additional experiment examin ed the ability of MK-801 to block the induction of sensitization by re peated d-amphetamine. In this experiment, rats were administered salin e or MK-801 (0.25 mg/kg IP) 15 min before each of ten amphetamine inje ctions (1.0 mg/kg IP, administered under the same regimen as immobiliz ation stress). Four days after the final immobilization or amphetamine injection, rats were tested for locomotor response to novelty, saline and d-amphetamine (1.5 mg/kg IP). Exposure to repeated immobilization stress significantly enhanced the locomotor response to amphetamine c hallenge but not to saline challenge whether rats were pretreated with saline, MK-801 or haloperidol. Secondary analysis of dose effects in each pretreatment group revealed that at 0.25 mg/kg, repeated MK-801 i n itself induced sensitization to the response to amphetamine in contr ol rats and potentiated stress-induced sensitization in restrained rat s. In contrast, the sensitization induced by repeated amphetamine was attenuated by MK-801 pretreatment. Neither dose of haloperidol affecte d the locomotor response to saline or amphetamine in control or stress ed rats. These results indicate that the effects of MK-801 on the indu ction of sensitization are complex and suggest that amphetamine- and s tress-induced behavioral sensitization may arise through different mec hanisms.