Prenatal methylazoxymethanol treatment potentiates d-amphetamine- and methylphenidate-induced motor activity in male and female rats.
The effects of the stimulant drugs, d-amphetamine and methylphenidate, upon the motor activity of male and female off-spring of pregnant rats, treated on gestation day 15 with the antimitotic agent methylazoxymethanol (MAM, 25 mg/kg) were studied in four experiments. Cortical and striatal hypoplasia induced by prenatal administration of MAM resulted in increased concentrations of catecholamines in those regions. Administration of d-amphetamine and methylphenidate caused significant increases in motor activity; this effect was markedly potentiated in the MAM-treated rats, both the male and female off-spring. Thus, the locomotion and total activity parameters showed similar, but not identical, drastic increases in behaviour induced by the stimulant drugs as a result of the prenatal MAM treatment whereas for the rearing parameter a lesser potentiation by the MAM treatment was observed. This potentiation of the excitatory effects of the stimulant compounds upon the behavioural parameters is interpreted in terms of a relative increase in the density of catecholaminergic terminals in the forebrain regions of the central nervous system. The present results are discussed with regard to the utility of prenatal MAM treatment as a possible animal model for certain neurological disorders.
Archer
T
T
R & D Laboratories, Astra Alab AB, Södertälje, Sweden.
Fredriksson
A
A
Sundström
E
E
Luthman
J
J
Lewander
T
T
Söderberg
U
U
Jonsson
G
G
D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000139:chemically induced; D001391:Azo Compounds / Q000633:toxicity*; D003913:Dextroamphetamine / Q000494:pharmacology*; D004195:Disease Models, Animal; D004357:Drug Synergism; D005260:Female; D005333:Fetus / Q000187:drug effects*; D008297:Male; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives / Q000633:toxicity*; D008774:Methylphenidate / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects
D001391:Azo Compounds; D011954:Receptors, Dopamine; D008774:Methylphenidate; D008746:Methylazoxymethanol Acetate; C030667:methylazoxymethanol; D003913:Dextroamphetamine