Effects of nimodipine and nifedipine upon behavior and regional brain monoamines in the rat.
The effects of single and repeated (9 times) administration of two dihydropyridines (DHPs), nimodipine (NIM) and nifedipine (NIF) (5 mg/kg per 12 h and 2.5 mg/kg per 12 h, IP), on the behavior of male adult rats in the holeboard and in the plus-maze, were investigated. Besides, the effects of repeated administration of the drugs on the levels of dopamine (DA), serotonin (5-HT), and their respective major metabolites in several regions of the central nervous system (CNS) were also assessed. The effects of single and repeated administration of the drugs were similar. Both DHPs caused a significant decrease in general motor activity which was evident in both tests and more marked, with the higher doses. The two exploratory parameters measured in the holeboard, i.e. head-dipping frequency and duration, were dissociated under pharmacological treatment. The drug-treated animals did not show an increased emotionality in the holeboard. However, in the plus-maze, NIF (5 mg/kg) and to a lesser extent NIM, appeared to induce some anxiety-related responses which may be secondary, at least in part, to the depressing effect on activity and exploration. Repeated administration of NIM and NIF caused an increase in striatal DA and DOPAC levels, whilst no effects were found on serotonergic system in any of the regions of the CNS analyzed.
Departmento de Biologia Animal II Facultad de Biologia, Universidad Complutense, Madrid, Spain.
M P
MP
Viveros
S
S
Martín
M J
MJ
Ormazabal
M J
MJ
Alfaro
M I
MI
Martín
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004298:Dopamine / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D006719:Homovanillic Acid / Q000032:analysis; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D009553:Nimodipine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000032:analysis*
D002121:Calcium Channel Blockers; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D009553:Nimodipine; D009543:Nifedipine; D004298:Dopamine; D006719:Homovanillic Acid