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Cognitive impairment and cerebral atrophy in “heavy drinkers”

1. Aim of the work was to verify the following three hypotheses in alcoholics: a) right hemisphere; b) diffuse brain deficit; c) anterior brain deficit, by means of a neuropsychological and a neuroradiological assessment. 2. 15 alcoholic right-hand male subjects and 15 matched controls were enrolled in the study. 3. Specifically designed neuropsychological testing was performed to investigate logical abilities, selective attention and memory. 4. Neurological investigation was performed by a standard CT scan to assess the degree and localization of brain damage. 5. Alcoholics performed worse than controls on some neuropsychological tests, i.e. Attention Matrices Test, Verbal Judgement Test, Forward Digit Span, Story Recall and Remote Memory Test. The analysis of variance adjusted by the attentional score showed no significant differences between alcoholics and controls. 6. Neuroradiological data showed a preeminent and a more frequent atrophy of the frontal region. 7. No correlations emerged between neuropsychological and neuroradiological data. 8. In conclusion, the hypothesis of anterior brain deficit seems to be confirmed by our study.

Synchronization of the EEG and sedation induced by neuroleptics depend upon blockade of both D1 and D2 dopamine receptors

Blockade of dopamine (DA) receptors by neuroleptics tends to produce sedation, as shown by increased sleeping time, reduction of the arousal response to sensory stimuli and slowing of the electrical (EEG) activity of the brain. The EEG and behavioural effects of the selective compounds, SCH 23390 and raclopride, which block either D1 or D2 receptor subtypes, respectively were evaluated. Groups of rabbits were prepared for the measurement of EEG activity (neocortex and hippocampus). The EEG was analyzed visually and by spectral power analysis. Gross behaviour was also observed. The D1 antagonist, SCH 23390, by itself (0.03-0.3 mg/kg i.v.) produced small changes in the EEG and no evidence of sedation. Periods of slow waves occurred sporadically. Computerized EEG analysis showed moderate increases of total power density. The D2 receptor blocker, raclopride, alone (1-3 mg/kg i.v.) produced changes of the activity of the EEG, mostly, short periods of slow waves and slight increases of total power. No sedation was noted. Although both selective antagonists were studied at larger doses than those minimally effective, they produced slight EEG and behavioural changes which were not comparable with the marked actions produced by classical neuroleptics, such as haloperidol. However, when raclopride (1 mg/kg) was given after treatment with SCH 23390 (0.03 mg/kg) there was a marked synchronized activity in the EEG, associated with a state of sedation and diminished responsiveness to sensory stimuli. The data indicate that EEG synchronization and sedation, classically associated with treatment with neuroleptics, do not depend upon the selective blockade of either D1 or D2 receptors but, instead, require concurrent blockade of both subtypes of receptor.

Role of dopamine D-1 and D-2 antagonists in a model of focal epilepsy induced by electrical stimulation of hippocampus and amygdala in the rabbit

1. The differential role played by blockade of D-1 or D-2 dopamine receptors in mechanisms underlying seizures was studied in a model of EEG after-discharge induced by electrical stimulation of selective brain regions (dorsal hippocampus and amygdala) in the rabbit. 2. The D-2 antagonist haloperidol (1 mg/Kg) increased significantly after-discharge duration after stimulation of either hippocampus or amygdala and lowered after-discharge threshold in few animals. 3. The D-1 antagonist SCH 23390 (0.3 mg/Kg) caused no changes following stimulation of amygdala and reduced after-discharge duration when hippocampus was stimulated. 4. Haloperidol exerted a proconvulsant action in this experimental model, having a clearer influence on D-2 receptors. SCH 23390 had no effect on amygdala whereas it exerted protection on the hippocampus. 5. The present data suggest that D-1 and D-2 receptors have different roles in generating and spreading the epileptic activity.

Centrally administered N-terminal fragments of ACTH (1-10, 4-10, 4-9) display convulsant properties in rabbits.

Electroencephalographic and behavioral effects of the following ACTH fragments: 1-4, 4-9, 4-11, 1-10, 4-10, 1-13, 1-17 and 1-24 were studied in rabbits. Sequences 4-9, 1-10 and 4-10 displayed some epileptic properties, i.e., they induced epileptic seizures (only electrographic or also behavioral) or increased hippocampal spiking. The 4-9 sequence seemed to be the common sequence responsible for these proconvulsant effects. The possible involvement of the enkephalinergic system is discussed.

Effects of remoxipride, a dopamine D-2 antagonist antipsychotic, on sleep-waking patterns and EEG activity in rats and rabbits

The antipsychotic remoxipride, a selective dopamine D-2 receptor antagonist, was studied for its effects on sleep-waking patterns in the rat and electroencephalographic (EEG) activity in the rabbit. Haloperidol, which has lesser selectivity for D-2 receptors, was used for comparison. In the rat, remoxipride (1–10 mg/kg SC) did not affect either total sleep or non-rapid eye movement (non-REM) sleep. Only REM was slightly reduced by the high dose of 10 mg/kg. Haloperidol (0.1–1 mg/kg PO) enhanced duration of both total sleep and non-REM sleep. In the rabbit, remoxipride (3 and 10 mg/kg IV) induced no significant changes of the EEG power spectrum over 0.1–38.5 Hz or individual frequency bands. In both cortex and hippocampus the drug did not alter the arousal response to acoustic sensory stimuli. Plasma concentration of remoxipride 10 mg/kg IV in rabbits declined biexponentially and was 4 and 2 µmol/1 at 30 min and 1 h, respectively. Haloperidol (0.3 and 1 mg/kg) slowed down the EEG activity, enhanced the power spectrum of the cortical and hippocampal activity, and significantly reduced the duration of arousal induced by sensory stimuli. The results indicate that, unlike haloperidol, remoxipride has weak or no sedative effects. The data also provide support to the notion that D-2 receptors are not involved in the regulation of states of sleep and sedation.

EEG and behavioural effects of polyamines (Spermine and Spermidine) on rabbits

The EEG and behavioural changes induced by the administration of polyamines (spermine and spermidine) were studied in rabbit. Spermine and spermidine were administered at different doses (200 and 400 micrograms) into the mesencephalic ventricle (i.c.v.) both as a bolus and in constant perfusion (60 min duration). We also studied the effects of methamphetamine (MA) in a group of rabbits pretreated with spermine and spermidine 200 and 400 micrograms i.c.v. as bolus. Spermine caused a dose-related cortical synchronization associated with a partial sedation; spermidine induced cortical synchronization at a low dose without any behavioural changes while at higher dose (after perfusion) cortical desychronization with an arousal behavioural pattern occurred. The possible interaction of these substances with the mesolimbic dopaminergic system is discussed on the basis of their potential neuroleptic action.

Neuropeptides and cerebral electric activity in rabbits

The effects of some neuropeptides infused into the cerebral ventricles on the spontaneous cerebral electric activity were studied in unanasthetized rabbits. The following peptides were investigated: physalaemin, caerulein, bombesin, litorin (supplied by Farmitalia). The rabbits were prepared according to Monnier and Gangloffs [10] method in order to record the spontaneous cortical activity. Each of these substances affects the electroencephalographic (EEG) records in a specific and dose-related way. Bombesin induces a biphasic pattern (synchronization followed by a partial activation), litorin is partially activating and physalaemin brings about a marked desynchronization. In spite of the marked structural analogy between bombesin and litorin, their EEG effects differ.

Comparative study of the EEG profile of neuroleptics selective for D-1 or D-2 dopamine receptors in the rabbit

The neuroleptics SCH 23390 and raclopride, which interact selectively with either D-1 or D-2 dopamine receptor, were studied for their effects on electroencephalographic (EEG) activity in the rabbit. Haloperidol (0.3 and 1 mg/kg intravenously, i.v.), which was used for comparison, induced synchronization of the cortical EEG activity. Spectral EEG analysis showed increase of power in the whole frequency range (0.1-38.5 Hz) and in all frequency bands in the cortex, whereas a slight decrease of slow and fast theta activity (3.7-7.2 and 7.2-12.2 Hz) was observed in the hippocampus. Animals appeared sedated and arousal response to somatosensory stimuli was markedly inhibited. SCH 23390 (0.03 and 0.3 mg/kg i.v.) induced periods of cortical synchronization and changes of spectral power qualitatively similar to those accompanying haloperidol administration. The drug slightly reduced the duration of arousal elicited by stimuli. Raclopride (1 and 3 mg/kg i.v.) induced weak EEG changes and little effect on arousal response to stimulation. There was an increase of slow wave activity which was particularly evident in the hippocampus. The data indicate that, although to a lesser degree, the D-1 receptor antagonist SCH 23390 induced EEG effects similar to those of haloperidol, whereas blockade of D-2 receptors by raclopride resulted in different patterns of EEG activity.

Eegraphic and behavioural effects of ondansetron, a 5HT3 antagonist, in rabbits

1. EEGraphic and behavioural effects of ondansetron, a 5HT3 antagonist, have been studied in the rabbit. Subsequently we tested the neurophysiological and behavioural interactions between ondansetron and L-5-HTP induced serotonergic syndrome. 2. The drug produced a dose-dependent (0.001, 0.01, 0.1 mg/kg i.v.) increase in the cortical power density spectrum, particularly in the range of the lowest frequencies bands. This effect is expression of cortical synchronization. 3. The lowest and mild dose, but not the highest, failed to produce behavioural sedation and to inhibit the arousal induced by vibroacustical stimulation. 4. L-5-HTP (10 mg/kg i.v.) administration generated a typical EEGraphic-behavioural pattern characterized by a decrease of cortical power spectrum density and stereotyped movements. The EEGraphic effects were significantly suppressed by administration of mild and higher doses of ondansetron, while the behavioural effects were inhibited by all doses tested. 5. It is concluded that ondansetron acts with considerably efficacy on central nervous system. The administration of low and mild doses shows a singular dissociation between EEGraphic and behavioural actions. The inhibition of the L-5-HTP behavioural syndrome by ondansetron suggests that this drug acts on behaviour only when there is an altered physiological pattern.

Centrally administered VIP increases spindle activity in unanaesthetized rabbits

The action of VIP on structures responsible for cerebral electrical activity has been investigated in unanesthetized rabbits. VIP was given by slow infusion or bolus into the mesencephalic ventricle or the carotid artery, and topically applied on the motor or visual cortex. Both intracerebroventricular and intracarotid administration induced an increase of spindle activity of the cortex and an inhibition of the strychnine-transmitted spikes. These findings suggest a possible inhibitory role for VIP on certain CNS activity.