Early changes in the development of dopaminergic neurotransmission after maternal exposure to cannabinoids.
Perinatal exposure to cannabinoid derivatives has been shown to affect brain development. In this work, we studied the changes induced by maternal exposure to cannabinoids during gestation and lactation on the dopaminergic activity in the prosencephalic area of offspring of several days of development. This brain area contains an increasing population of dopaminergic terminals from the different dopaminergic pathways that become differentiated in the adult rat. We measured the endogenous content of dopamine and its intraneuronal metabolite, L-3,4-dihydroxyphenylacetic acid, and the activity of tyrosine hydroxylase as indices of dopaminergic activity. Results showed that perinatal exposure to cannabinoids caused several changes in the evolution of the dopaminergic indices studied. These changes were mainly observed in males. The only alteration in females occurred on the tenth day of development: An increase in dopamine content was observed with no changes in either the content of L-3,4-dihydroxyphenylacetic acid or tyrosine hydroxylase activity. In males, the content of both dopamine and L-3,4-dihydroxyphenylacetic acid were decreased on the day previous to birth in the animals exposed to cannabinoids. Although the reduction in its metabolite disappeared on the fifth day, the decrease in dopamine was maintained and it was correlated with a decrease in tyrosine hydroxylase activity. However, this decrease in the activity of tyrosine hydroxylase was followed by an increase on the tenth day. These results allow us to conclude that perinatal exposure to cannabinoids produces changes in the normal development of several indices of the activity of dopaminergic neurons in the brain area containing the most important population of dopaminergic endings. These changes were mainly observed in males. They could be responsible for a long-term alteration in the neurological processes in which these neurons are involved in the adult.
Department of Biochemistry, Faculty of Medicine, Complutense University, Madrid, Spain.
F
F
Rodríguez de Fonseca
M L
ML
Hernández
R
R
de Miguel
J J
JJ
Fernández-Ruiz
J A
JA
Ramos
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D002186:Cannabinoids / Q000633:toxicity*; D004298:Dopamine / Q000502:physiology*; D005260:Female; D007774:Lactation; D008297:Male; D008431:Maternal-Fetal Exchange; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D012727:Sex Characteristics; D009435:Synaptic Transmission / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002186:Cannabinoids; D015102:3,4-Dihydroxyphenylacetic Acid; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine