In utero alcohol and postnatal methylphenidate: locomotion and dopamine receptors.
Prenatal alcohol exposure can cause central nervous system abnormalities and dysfunction referred to as Alcohol-Related Neurodevelopmental Disorder (ARND). Repeated intermittent methylphenidate (Ritalin) was used as a psychopharmacological challenge to reveal functional alterations in dopamine binding sites in rats exposed prenatally to alcohol. Pregnant Long-Evans dams were intubated with 0, 3, or 5 g/kg/day of alcohol from gestational day (GD) 8 to GD20. Adult offspring received repeated intraperitoneal injections of 0, 4, or 8 mg/kg of methylphenidate (MET), and were tested periodically for locomotor activity. Autoradiographic assessment of dopamine D1 and D2 receptors binding were visualized using [3H]SCH 23390 and [3H]raclopride, respectively. Prenatal alcohol did not produce significant dose-dependent effects on adult locomotor activity. Repeated MET injections produced dose-dependent sensitization of locomotor activity in all groups. The 3-g/kg prenatal alcohol group had a significantly decreased number of dopamine D2 binding sites within the dorsal and ventral striatum. This effect was reversed by MET. The neural changes detected in the lower alcohol group may indicate persistent changes within the dopaminergic system due to prenatal alcohol exposure.
Randall
S
S
Department of Psychology, Wayne State University, Detroit, MI 48201, USA.
Hannigan
J H
JH
D000818:Animals; D001552:Benzazepines / Q000378:metabolism; D001665:Binding Sites; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D020891:Raclopride / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D020318:Rats, Long-Evans; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D014316:Tritium
D001552:Benzazepines; D018765:Dopamine Uptake Inhibitors; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D014316:Tritium; D008774:Methylphenidate; D000431:Ethanol; D020891:Raclopride