Effects of unilateral labyrinthectomy on the norepinephrine content in forebrain and cerebellar structures of albino rats.

ABSTRACT

Albino (Wistar) rats were used to investigate whether unilateral labyrinthectomy (UL) modified the concentration of norepinephrine (NE) as well as of dopamine (DA) and the corresponding metabolite 3, 4-dihydroxyphenylacetic acid (DOPAC) in different areas of the cerebral and the cerebellar cortex and the striatum. The results obtained in 38 rats submitted to UL were compared to those of 18 rats submitted to sham-operation. The animals were operated under sodium pentobarbital anesthesia and sacrificed 1.5, 3 and 6 h after surgery. All rats submitted to UL showed phenomena of deficit (1.5-3 h after the lesion) followed by partial vestibular compensation (3-6 h after the lesion). Significant changes in the content of NE were neither found in different areas of the cerebral and the cerebellar cortex, nor in the striatum of rats sacrificed 1.5 h after UL. Three h after the lesion a bilateral increase in the NE content occurred in all the explored areas of the cerebral cortex (i.e., frontal, parieto-temporal and occipital) and the cerebellar cortex (i.e., the vermis and flocculus), as well as in the striatum. This increase, however, was more prominent in the parieto-temporal areas of the neocortex of the intact side, in all the explored areas of the cerebellar cortex of that side, as well as in the striatum of the lesioned side. This asymmetric increase in NE content could not be attributed, at least exclusively, to a generalized activation of the noradrenergic LC nuclei of both sides, due to waking and/or stress which may occur after UL, but did rather depend on asymmetric changes in unit discharge of the vestibular nuclei projecting to the LC of both sides, following UL. In particular, the increased discharge of the vestibular nuclei of the intact side would lead to activation of noradrenergic neurons projecting particularly to the parieto-temporal cortex and the cerebellar cortex of the intact side, as well as to the striatum of the lesioned side. A bilateral increase in NE content was still observed in different areas of the cerebral and cerebellar cortex of rats sacrificed 6 h after UL. This increase, however, was of smaller entity than that observed in the same areas 3 h after UL and quite symmetric. The content of DA and its metabolite DOPAC decreased bilaterally in the striatum of rats sacrificed 1.5 h after UL. This effect was attributed to a reduced synthesis and release of DA, which probably resulted from a reduced facilitatory influence that the deafferented vestibular nuclei exert on the dopaminergic, nigrostriatal system of both sides, although mainly on the intact side. The corresponding values, however, bilaterally recovered to slightly increase with respect to the control values in rats sacrificed 3 and 6 h after UL. In these experiments the content of both DA and DOPAC remained symmetric on both sides after UL, in contrast with the bilateral but asymmetric increase in NE concentration observed in the same structure 3 h the lesion. The present results integrate and extend those of previous experiments showing that 1) albino rats sacrificed 6 h after UL displayed an increased synthesis of NE, which affected particularly the LC of the intact side as well as the medial vestibular nuclei of both sides (21); and 2) the structures which showed an increased content of NE at given time intervals after UL also displayed an increase in the expression of the immediate early gene c-fos (cf. 16 for ref.). These findings suggest that bilateral but asymmetric activation of the noradrenergic LC neurons following UL may lead to an asymmetric increase in c-fos expression in several target structures, thus contributing to the plastic changes responsible for vestibular compensation. In conclusion, it appears that UL induces in several brain structures of albino rats a short-term increase in synthesis and release of NE. (ABSTRACT TRUNCATED)