Studies on neurotensin catecholamine interactions in the hypothalamus and in the forebrain of the male rat

Abstract

Neurotensin (NT)-catecholamine (CA) interactions have been characterized at the pre- and post synaptic level in the hypothalamus and the forebrain by a combined morphometrical, receptor autoradiographical, biochemical and quantitative microfluorimetrical analysis as well as by radioimmunoassay determinations of serum levels of adenohypophyseal hormones. | 1. (1) The morphometrical analysis demonstrated an overlap of NT and TH immunoreactive areas in the lateral palisade zone (LPZ) of the ME. These results were compatible with the view that NT may be a comodulator in dopamine (DA) nerve terminals in the LPZ but only in a restricted DA terminal population. 2. (2) The receptor autoradiographic analysis on [ 3H]NT binding sites using a concentration of 4 nM shows a very weak labelling of the median eminence possibly due to the presence of NT receptors of a very high affinity type. 3. (3) Intraventricular injections of NT in the awake unrestrained male rat in the dose range of 0.06–6 nmol selectively increased noradrenaline (NA) utilization and turnover in the subependymal layer and in the medial palisade zone (MPZ) of the median eminence (ME) and did not change DA levels and turnover in the ME. 4. (4) Intraventricular injections of NT (0.06–6 nmol) produced a dose dependent depletion of NA stores in preoptic suprachiasmatic and periventricular NA nerve terminals. This action was not associated with any change of NA utilization in these NA nerve terminals. 5. (5) Intraventricular injections of NT (6 nmol) produced a selective increase of NA stores in the dorsomedial hypothalamic nucleus, a change which was not associated with a change in NA utilization. 6. (6) Intraventricular injections of NT produced dose-dependent and selective increases of DA utilization in the cholecystokinin positive and negative nerve terminal systems of the nucleus accumbens. 7. (7) Intraventricular injections of NT (0.06–6 nmol) dose dependently reduced the prolactin, TSH and LH secretion and increased ACTH secretion. Their relationship to the CA turnover changes demonstrated is discussed. 8. (8) In in vitro experiments NT (10 nM) could not significantly modulate the binding characteristics of [ 3H]spiperone labelled dopamine receptors of the D2 type in subcortical limbic membranes. These new findings are discussed also in relation to the hypothermic and behavioural effects of NT as well as its possible role in schizophrenia.