A. Quattrone

Effect of midbrain raphe lesion or 5,7-dihydroxytryptamine treatment on the prolactin-releasing action of quipazine andd-fenfluramine in rats

The role of brain serotonin in regulating prolactin (PRL) secretion has been investigated by studying the effect of quipazine and D-fenfluramine, two serotonin-like drugs, on plasma PRL levels under various experimental conditions. Quipazine (5, 10 and 20 mg/kg i.p.) and D-fenfluramine (5, 7.5 and 10 mg/kg i.p.) induced dose-related increases in plasma PRL levels in male rats. Intraventricular injection of 5,7-dihydroxytryptamine (5,7-DHT) or electrolytic lesion of the nucleus raphe medianus (MR), which caused a marked and selective depletion of hypothalamic serotonin levels, significantly reduced the PRL-releasing effect of both quipazine and D-fenfluramine. These results suggest that the effect of these drugs on PRL release is mediated through a serotonergic mechanism in the brain.

Increased GH responsiveness to dopamine receptor stimulation in alcohol addicts during the late withdrawal syndrome

In humans the release of growth hormone (GH) elicited by dopamine (DA) and DA agonists may represent a reliable model to assess change in sensitivity of DA receptors. We now report that in chronic alcoholics, 4-7 days after the suspension of alcohol consumption, the increase of GH response to DA infusion was higher than that seen in non alcoholic volunteers. The specificity of this GH response to DA administration was demonstrated by the use of domperidone, a novel peripheral antagonist of DA receptors. These results suggest the development of hyper-responsiveness of DA receptors involved in the control of GH secretion in chronic alcoholics during the later phases of the withdrawal syndrome.

Different susceptibilities of the geniculate and extrageniculate visual pathways to human Creutzfeldt-Jakob disease (a combined neurophysiological-neuropathological study)

Flash evoked visual potentials (FEPs) of 7 patients with advanced Creutzfeldt-Jakob disease (CJD) were compared with those recorded in 7 patients with senile dementia of the Alzheimer type (SDAT), in 13 age- and sex-matched healthy volunteers and in 7 neuropsychiatrically normal subjects whose occipital evoked responses were increased in amplitude (amplitude controls). Post-mortem examination was performed in 4 of 7 CJD patients in order to map pathological changes along the visual pathways, including the retino-geniculo-striate and extrageniculate pathways. Normal FEPs were typified by 2 constant early components (P1 and N2) followed by several (3 or more) late components that were characterized by marked interindividual variability. Amplitude controls had enlarged (from 14 to 44.8 microV, mean 25.7) P1 component. Both SDAT and CJD patients had normal early FEP waves (P1 and N2) and important alterations of the late FEP components. Moreover, a late positive component was responsible for abnormally enlarged FEPs (52.6 and 58.2 microV) in 2 CJD patients. Finally, electroretinograms, recorded in 1 CJD patient, were normal. These findings suggested relative functional integrity of the retino-geniculo-striate pathway associated with important dysfunction of the cortical visual processing in both SDAT and CJD patients. Pathological studies disclosed preservation of optic nerves, chiasmas, lateral geniculate nuclei and Gennaris strip of the striate cortex but associated with important spongiform change, neuronal loss and gliosis in the superior colliculi (layer II), pulvinar, extrastriate cortex and layers II-III, V and VI of the striate cortex. We conclude that different visual pathways have different susceptibilities to CJD: important functional and anatomical alterations of the intracortical and extrageniculate pathways contrast with relative preservation of the retino-geniculo-striate pathway.

Effect of selective degeneration of brain serotonin-containing neurons on plasma corticosterone levels: Studies with d-fenfluramine

Summary The effect of selective lesion of brain serotonergic neurons on the corticosterone releasing action of d-fenfluramine were studied in male rats. Raphe lesion, which selectively decreased brain 5-HT, prevented the effect of the d-fenfluramine on corticosterone secretion. An intraventricular injection of 5,7-dihydroxytryptamine, in desipramine-pretreated rats, which caused a substantial damage to central serotonergic systems without affecting catecholamine-containing neurons, also blocked the stimulatory effect of d-fenfluramine on corticosterone release. These findings are compatible with the hypothesis that brain 5-HT plays a stimulatory role in the control of hypothalamic-hypophyseal-adrenal axis in the rats.

Nonmetabolic causes of triphasic waves : a reappraisal

Two more patients with triphasic waves (TW) on their EEGs in the absence of metabolic disturbances are described. One patient had coma associated with cerebellar hematoma, the other had mild dementia associated with idiopathic calcifications of the basal ganglia and normal auditory brainstem responses, subcortical and cortical somatosensory evoked potentials. Neurologic examination failed to show asterixis in both patients. The literature on nonmetabolic causes of TW was also reviewed, and the clinical and anatomic reports of 10 patients have been analyzed: 7 patients had focal brainstem-diencephalic lesions (craniopharyngioma: 2 patients; thalamic gliomas: 3 patients; pontine stroke: 2 patients), and 3 patients suffered from diffuse subcortical or multifocal encephalopathies (Binswangers encephalopathy: 1 patient; cerebral carcinomatosis: 1 patient; multifocal cerebral lymphoma: 1 patient). From the clinical point of view, patients with nonmetabolic diseases causing TW presented either disturbance of higher cerebral functions with no asterixis or sudden onset of coma. It is concluded that TW may result from focal brainstem/diencephalic lesions or from diffuse subcortical or multifocal encephalopathies in the absence of concomitant metabolic abnormalities. Nonmetabolic causes of TW should be suspected in patients presenting with neurologic disturbances not associated with asterixis.

Effect of quipazine and d-fenfluramine, two serotonin-like drugs, on TSH secretion in basal and cold stimulated conditions in the rat

Abstract The effects of two serotonin-like drugs, quipazine and d-fenfluramine, on thyroid stimulating hormone (TSH) secretion in basal and cold stimulated conditions were investigated in male rats. Both drugs are able to decrease TSH secretion in basal conditions and to inhibit the TSH rise elicited by cold exposure (CE). These effects were antagonized by a pretreatment with metergoline, a serotonin receptor blocker. These results appear to suggest that serotonin may play an inhibitory role in the control of TSH secretion in the rat.

Release of endogenous dopamine from tuberoinfundibular neurons

Release of endogenous dopamine(DA) from arcuate-periventricular nucleus-median eminence fragments has been analyzed in an in vitro static incubation system. Exposure of these hypothalamic fragments to increasing concentrations of K+ ions produced a dose-dependent release of endogenous DA. The highest rate of K+-stimulated DA efflux occurred in the first 10 minutes, thereafter it progressively declined reaching prestimulated levels at 30 minutes. If two consecutive depolarizing stimuli of 40 mM KCl were applied to the same hypothalamic fragment, after a 40 minutes rest period, an equivalent release of endogenous DA occurred. Removal of Ca++ ions from the incubation medium containing the Ca++ chelator EGTA caused a decrease of basal DA efflux and completely prevented the K+-induced release of DA. Furthermore when verapamil, a blocker of Ca++ entrance, was added to the incubation medium in a concentration of 50 microM, the K+-induced DA efflux was completely counteracted, whereas spontaneous release was unmodified. Finally nomifensine, a potent blocker of DA uptake, added in vitro in a final concentration of 10 microM, significantly reinforced K+-induced release of endogenous DA. Since nomifensine did not modify basal DA release, this study confirmed its prevalent uptake blocking property rather than its releasing action on DA.

Effect of selective lesioning of serotonin-containing neurons on the TSH-inhibiting action of d-fenfluramine in male rats.

Abstract The effects of selective lesion of brain serotoninergic neurons on the TSH inhibiting action of d-fenfluramine were studied in male rats. Raphe lesion, which selectively decreased brain 5-HT, prevented the effect of d-fenfluramine on TSH secretion. An intraventricular injection of 5, 7-dihydroxytryptamine (150 μg in 20 μ1), in desipramine-pretreated rats, which caused a substantial damage to central serotoninergic systems without affecting catecholamine- containing neurons, also blocked the inhibitory effect of d-fenfluramine on TSH release. These findings are compatible with the hypothesis that brain 5-HT plays an inhibitory role in the control of TRH-TSH secretion in male rats.

Sensory evoked potentials in Creutzfeldt-Jakob disease.

Eight patients presenting with intermediate or terminal evolution of Creutzfeldt-Jakob disease (CJD) were investigated by means of evoked potentials. Fifteen age-matched healthy subjects served as controls. The 8 patients had well-recognizable but simplified flash evoked potentials (FEPs) consisting of P1 and N2 waves followed by a single late positive (P2) deflection. Enlarged FEPs were found in 2 of the 8 patients. The somatosensory central conduction time was normal in 3 of 5 patients, and it resulted in upper normal limits or was moderately slowed in 2 patients. No enlarged somatosensory scalp potentials were recorded. Cortical somatosensory responses were characterized by an unrecognizable (4 patients) or delayed (2 patients) N33 wave. Brainstem auditory evoked responses, recorded in 6 patients, were normal. In CJD very important functional impairment of the sensory cortical areas is associated with absent or mild dysfunction of the subcortical sensory pathways.

Combined Neurophysiological Studies in Creutzfeldt-Jakob Disease: A Case Report

EEG and brain mapping (on basal conditions and after i.v. administration of diazepam) and visual, somatosensory and auditory evoked potentials have been performed on a patient at terminal evolution of CJD. These combined neurophysiologic studies indicated that very important functional impairments of either thalamic-frontal circuits and frontal, parietal and occipital cortex were associated with absent or mild dysfunction of the visual, somatosensory and auditory subcortical pathways. Combined neurophysiologic studies are important to better understand the pathophysiologic mechanisms of neurodegenerative diseases.