Changes in brain dopaminergic indices induced by perinatal exposure to cannabinoids in rats.
Perinatal exposure to cannabinoid derivatives has been shown to produce effects on brain development. In this study, we evaluated the changes induced by maternal exposure to hashish crude extract (HCE) during gestation and lactation in several biochemical indices of dopamine activity in the striatum and the limbic forebrain of offspring. Studies were performed either during the HCE exposure or after drug withdrawal. Perinatal exposure to HCE reduced the number of striatal D1 binding sites in females and increased the L-3,4-dihydroxyphenylacetic acid/dopamine (DOPAC/DA) ratio, whereas an increase in the number of striatal D2 binding sites, with a reduction in their affinity, and a decrease in the activity of tyrosine hydroxylase (TH) were observed in males. The DOPAC/DA ratio was also increased in the limbic forebrain in HCE-exposed females, but there were no changes in binding site parameters. Most of these effects disappeared after cessation of cannabinoid treatment, but the decrease in striatal TH activity in males was maintained during drug withdrawal. Interestingly, the affinity of D2 receptors in the striatum of females, the number of striatal D1 receptors in males, and the limbic TH activity in males increased after the cessation of drug treatment. These results allow us to conclude that: (1) the effects of perinatal exposure to HCE were different depending on the sex and the specific brain area studied; and (2) most of the effects disappeared after cessation of cannabinoid treatment, although some new changes then appeared.
Rodriguez de Fonseca
F
F
Department of Biochemistry, Faculty of Medicine, Complutense University, Madrid, Spain.
Cebeira
M
M
Hernández
M L
ML
Ramos
J A
JA
Fernández-Ruiz
J J
JJ
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D002186:Cannabinoids / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012727:Sex Characteristics
D002186:Cannabinoids; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D004298:Dopamine