MOTOR BEHAVIOR AND NIGROSTRIATAL DOPAMINERGIC ACTIVITY IN ADULT-RATS PERINATALLY EXPOSED TO CANNABINOIDS

被引:70
作者
NAVARRO, M
DEFONSECA, FR
HERNANDEZ, ML
RAMOS, JA
FERNANDEZRUIZ, JJ
机构
[1] UNIV COMPLUTENSE MADRID,FAC MED,DEPT BIOCHEM,E-28040 MADRID,SPAIN
[2] UNIV COMPLUTENSE MADRID,FAC PSYCHOL,DEPT PSYCHOBIOL,E-28040 MADRID,SPAIN
关键词
MARIJUANA; CANNABINOIDS; DELTA-9-TETRAHYDROCANNABINOL; NIGROSTRIATAL DOPAMINERGIC NEURONS; DOPAMINE; DOPAC; TYROSINE HYDROXYLASE; D-1 AND D-2 RECEPTORS; MOTOR ACTIVITY; STEREOTYPIC BEHAVIOR;
D O I
10.1016/0091-3057(94)90110-4
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
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 D-1 and D-2 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 D-1 receptors. On the contrary, presynaptic activity in males perinatally exposed to hashish was unchanged, but there was an increase in the density of D-2 receptors, which tentatively might explain the increased stereotypy observed in males. Collectively, these results show that the changes in the ontogeny of nigrostriatal dopaminergic neurons originated by perinatal cannabinoid exposure: a) seem to be accompanied by subtle behavioral changes but only in immature males; and b) lead to a set of sexually dimorphic disturbances in the adult functionality of these neurons at the neurochemical and behavioral levels.
引用
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页码:47 / 58
页数:12
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