Differential effects of amphetamine and phencyclidine on the expression of growth-associated protein GAP-43.
The purpose of the present study was to test changes in the expression of growth-associated protein (GAP-43) after chronic treatment with two different psychotomimetic drugs: amphetamine and phencyclidine. Rats were treated chronically for 7 days (twice daily) with 5 mg/kg of amphetamine and phencyclidine and sacrificed after 2, 5 or 7 days of treatment, and following 7, 14 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 psychotomimetic drugs on the expression of GAP-43 we have used Northern blotting and quantitative in situ hybridization. Treatment with amphetamine induced decrease of GAP-43 mRNA expression, that was detected also during recovery period, 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 the first days of treatment until 21 days after the last day of treatment. Treatment with haloperidol did not produce significant changes in GAP-43 mRNA expression. It can be suggested that GAP-43 upregulation upon phencyclidine treatment occurs as a result of functional activation of pathways able to participate in remodeling, while amphetamine showed neurotoxic effect, decreasing expression of GAP-43 mRNA.
Vukosavic
S
S
Institute for Biological Research, 29 Novembar 142, Belgrade, Yugoslavia. selkan@ibissbg.ac.yu
Ruzdijic
S
S
Veskov
R
R
Rakic
L
L
Kanazir
S
S
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004334:Drug Administration Schedule; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D019922:GAP-43 Protein / Q000235:genetics*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010622:Phencyclidine / Q000494:pharmacology*; D011605:Psychoses, Substance-Induced / Q000378:metabolism* / Q000503:physiopathology; D011618:Psychotic Disorders / Q000378:metabolism* / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D015415:Biomarkers; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D019922:GAP-43 Protein; D012333:RNA, Messenger; D000661:Amphetamine; D010622:Phencyclidine; D006220:Haloperidol