Presynaptic alpha 2- and postsynaptic beta-adrenoceptor sensitivity in slices of rat neocortex after chronic treatment with various antidepressant drugs.

The effect of chronic (4 weeks) treatment of rats with the antidepressant drugs desipramine, maprotiline, chlorimipramine, zimelidine or iprindol on the sensitivity of presynaptic alpha 2- and postsynaptic beta-adrenoceptors in neocortical slices was investigated. Acute (1 day) treatment with the antidepressants did not affect the efflux of cyclic-AMP induced by isoprenaline (1 microM) from neocortical slices, while after chronic treatment the efflux of cyclic AMP was consistently reduced. Following acute administration the electrically-evoked release of [3H]noradrenaline (NA) from radiolabelled cortical slices remained unchanged. Upon chronic treatment with desipramine the release of [3H]NA was enhanced by about 45%. In contrast, after chronic treatment with maprotiline or chlorimipramine the electrically-evoked release of [3H]NA was not affected, whereas release was even slightly reduced after chronic administration of zimelidine or iprindol. In all cases, however, a similar inhibitory effect of exogenous NA (0.1 microM) on the release of [3H]NA was found. These data indicate that the desensitization of postsynaptic beta-adrenoceptors in rat brain after chronic treatment with antidepressant drugs is not paralleled by a reduction of presynaptic alpha 2-adrenoceptor sensitivity.

Immunocytochemical localization of dopamine in the prefrontal cortex of the rat at the light and electron microscopical level.

In the present study the dopaminergic innervation of the prefrontal cortex was studied by means of a recently developed anti-dopamine serum. This method can demonstrate endogenous dopamine in a specific way, and offers the opportunity to study the distribution of dopaminergic fibres in the cortex in detail in counterstained sections. Furthermore, dopaminergic nerve endings can be visualized at the electron microscopic level. Light microscopic observations demonstrated that the highest density of dopaminergic fibres in the frontal cortex is found in the prefrontal cortex and the infralimbic cortex. Within the prefrontal cortex, a good correlation is found between regional differences in distribution of dopaminergic fibres and the cytoarchitectonic parcellation of this part of the cortex. Outside the prefrontal cortex dopaminergic fibres were observed in adjacent frontal areas, the cortex surrounding the entire rhinal sulcus and the retrosplenial cortex. Electron microscopic observations demonstrated dopaminergic terminals through all cortical layers. The majority of dopaminergic terminals in the prefrontal cortex from synaptic contacts with dendritic processes. The synaptic profiles were usually symmetric and were characterized by the presence of many clear vesicles and an occasional dense-core vesicle.

Stereotaxic operation in the neonatal rat; a novel and simple procedure.

Since no simple method for standardized positioning of very young rats in a stereotaxic device has been described in the literature, a new method for stereotaxic placement in the neonatal rat was developed, which only requires a simple body mould of the rat pup, and a minor adaptation of a rabbit stereotaxic apparatus (Kopf). The costs of the materials needed for construction of the neonatal rat body mould were approximately $1.-. Construction of the body mould took about one hour. Reliability and accuracy of the new method are demonstrated in a series of experiments in which the A10 group of dopaminergic cell bodies in the ventral tegmental area of 1-day-old rats were lesioned bilaterally: 15 out of 20 angular electrode placements resulted in lesions, the centres of which were located within the A10 group of dopaminergic cell bodies in the ventral tegmental area (max. 0.8 mm in diameter).

Vasopressin fiber pathways in the rat brain following suprachiasmatic nucleus lesioning.

The contribution of the suprachiasmatic nucleus to the vasopressinergic innervation of the rat brain was determined by following the changes in the immunocytochemical localization of vasopressin-containing fibers at various intervals between 2 days and 12 weeks after bilateral lesioning of this nucleus. The disappearance of the vasopressinergic fibers makes it plausible that vasopressin-containing pathways run from the suprachiasmatic nucleus towards the periventricular nucleus, the dorsomedial nucleus of the hypothalamus and the organum vasculosum laminae terminalis. Since after lesioning the vasopressinergic fibers remained unaltered in the lateral septum, the lateral habenular nucleus, the nucleus of the amygdala, the diagonal band of Broca, the nucleus of the solitary tract, the interpeduncular nucleus and the dorsal raphe nucleus, the suprachiasmatic nucleus sends no or only minor projections to these areas. In contrast to the literature, these findings indicate that the paraventricular nucleus and possibly the supraoptic nucleus form the major source for vasopressinergic pathways in the brain.

The dopaminergic innervation of the supraoptic and paraventricular nucleus. A light and electron microscopical study.

An antiserum that has been raised against glutaraldehyde-conjugated dopamine was used to demonstrate specifically dopamine in the rat hypothalamus. This dopamine antiserum permitted an optimal fixation with glutaraldehyde and therefore enabled the simultaneous light and electron microscopic immunocytochemical localization of dopamine. It was demonstrated that the paraventricular and supraoptic nuclei of the hypothalamus were innervated by thin dopaminergic fibers, in contrast to the suprachiasmatic nucleus, which hardly received any dopaminergic input. Ultrastructural observations revealed that the dopamine fibers terminated synaptically on the magnocellular neurons and their processes. It is concluded that the present results may explain the effect of centrally injected dopamine on vasopressin and oxytocin release. In the dopamine-containing terminals the reaction product was frequently observed in 90 nm dense core vesicles and around clear vesicles.