Motor behavior and nigrostriatal dopaminergic activity in adult rats perinatally exposed to cannabinoids.
We have recently reported several neurochemical alterations, measured at perinatal and peripubertal ages, in the maturation of nigrostriatal dopaminergic neurons following perinatal hashish exposure. In the present work, we tried to undertake whether these neurochemical changes during ontogeny: a) were accompanied by changes of motor behavior, the main neurobiological process regulated by nigrostriatal dopaminergic neurons; and b) persisted in adulthood, leading to disturbances in the expression of an adult motor activity. To this end, two different experiments were performed. In the first, we examined, by using an actimeter, the ontogeny of spontaneous locomotor activity in immature male and female rats born from mothers perinatally exposed to hashish extract. Results showed a complete absence of significant changes in locomotor activity in females, whereas males presented a constant trend to decrease, although never statistically significant, at all ages studied as a consequence of the perinatal cannabinoid exposure. In the second experiment, we evaluated neurochemical indices--dopamine (DA) and L-3,4-dihydroxyphenylacetic acid (DOPAC) contents, tyrosine hydroxylase (TH) activity, and number and affinity of D1 and D2 dopaminergic receptors in the striatum--and behavioral parameters--spontaneous locomotor activity and spontaneous and induced stereotypic behavior--both indicating nigrostriatal dopaminergic activity, in adult female and male rats perinatally exposed to hashish extract. Results were as follows. The spontaneous locomotor activity, measured in the actimeter, was not affected by perinatal hashish exposure in both adult males and females. This was also seen in an open-field test as measured by total number of sector crossings. However, when differentiated between internal and external sectors hashish-exposed males presented a higher number of external crossings than controls, which did not appear in females. Moreover, several induced stereotypic behaviors, such as self-grooming and shaking induced by water spraying, were also altered by hashish treatment in a sexually dimorphic manner, whereas the number of spontaneous rears and self-grooms, measured in the open-field test, was unchanged. Thus, the frequency of water spraying-induced self-grooming was significantly increased in both males and females perinatally exposed to hashish, although the increase was more marked in males (200.4%) than females (121.2%). In addition, the frequency of shaking was also markedly increased in males but remained unchanged in females. These behavioral effects were paralleled by modifications in striatal neurochemical parameters. Thus, there was a significant increase in the DOPAC/DA ratio, indicating increased presynaptic activity, in females perinatally exposed to hashish, but compensated by a lower density of D1 receptors.(ABSTRACT TRUNCATED AT 400 WORDS)
Navarro
M
M
Department of Psychobiology, Faculty of Psychology, Complutense University, Madrid, Spain.
Rodríguez de Fonseca
F
F
Hernández
M L
ML
Ramos
J A
JA
Fernández-Ruiz
J J
JJ
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000375:Aging / Q000523:psychology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D002186:Cannabinoids / Q000494:pharmacology*; D002188:Cannabis; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002186:Cannabinoids; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D015102:3,4-Dihydroxyphenylacetic Acid; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine