Differential effects of amphetamine and phencyclidine on the expression ofgrowth-associated protein GAP-43

The purpose of the present study was to test changes in the expression of g rowth-associated protein (GAP-43) after chronic treatment with two differen t psychotomimetic drugs: amphetamine and phencyclidine. Rats were treated c hronically for 7 days (twice daily) with 5 mg/kg of amphetamine and phencyc lidine and sacrificed after 2, 5 or 7 days of treatment. and following 7, 1 4 or 21 days of recovery after full treatment (7 days). Separate groups of rats were treated on the same regiment with haloperidol, and control group was treated with vehicle. To determine the effects of different psychotomim etic drugs on the expression of GAP-43 we have used Northern blotting and q uantitative in situ hybridization. Treatment with amphetamine induced decre ase of GAP-43 mRNA expression. that was detected also during recovery perio d, up to 14 days after the last day of 7 days treatments. On the contrary, PCP induced increase of GAP-43 mRNA expression, that was detectable from th e first days of treatment until 21 days after the last day of treatment. Tr eatment with haloperidol did not produce significant changes in GAP-43 mRNA expression. It can be suggested that GAP-43 upregulation upon phencyclidin e treatment occurs as a result of functional activation of pathways able to participate in remodeling, while amphetamine showed neurotoxic effect, dec reasing expression of GAP-43 mRNA. (C) 2001 Elsevier Science Ireland Ltd an d the Japan Neuroscience Society. All rights reserved.