• Energy Research
• Closed Access close
• US close
• GB close
• DE close
• Neuroscience close

Effects of nicotine, administered by continuous infusion via osmotic minipumps, were studied on the operant self-administration of alcohol by rats, using a variable interval (15 s) schedule, and measuring the acquisition, maintenance, extinction and reinstatement of responding for alcohol. Doses of nicotine of 0.25, 1.25 and 7.5 mg/kg/24 h had no significant effects on the maintenance of responding for alcohol, but 5 mg/kg/24 h nicotine resulted in a significant increase in responding on the lever delivering the reward when water was substituted for the alcohol, indicating delayed extinction of responding. During infusion of 2.5 mg/kg/24 h nicotine, responding was significantly greater over the "sucrose-fading" training sessions, during acquisition of responding, when mixtures of alcohol and sucrose were provided as reward. When minipumps infusing 2.5 mg/kg/24 h nicotine were implanted after the alcohol responding had been acquired, the responding for alcohol increase during the first week of nicotine infusion, but corresponding nicotine infusion doses of 0.25, 1.25 and 7.5 had no significant effects. The results indicate that nicotine can increase operant responding for alcohol and this is crucially dependent on the dose of nicotine and the time of testing. The results have implications for the frequently encountered dependence on the combination of alcohol and nicotine.

Chronic exposure to ethanol can cause deficits in learning and memory. It has been suggested that withdrawal is potentially more damaging than the ethanol exposure per se. Therefore, we explored the effect of repeated episodic exposure to ethanol on key regulators of cortical activity, the neurotrophins. Rats were exposed to ethanol via a liquid diet for 3 days per week for 6-24 weeks. Control rats were pair-fed an isocaloric liquid diet or ad libitum fed chow and water. The concentrations of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) were determined using enzyme-linked immunosorbant assays (ELISAs). Five telencephalic structures were examined: parietal cortex, entorhinal cortex, hippocampus, the basal nucleus, and the septal nuclei. All five areas expressed each of the three neurotrophins; BDNF was most abundant and NGF the least. The parietal cortex was susceptible to ethanol exposure, NGF and BDNF content increased, and NT-3 content fell, whereas no changes were detectable in the entorhinal cortex. In the hippocampus, the amount all three neurotrophins increased following episodic ethanol exposure. Neurotrophin content in the two segments of the basal forebrain was affected; NGF and NT-3 content in the basal forebrain was reduced and NGF and BDNF content in the septal nuclei was increased by ethanol exposure. In many cases where ethanol had an effect, the change was transient so that by 24 weeks of episodic exposure, no significant changes were evident. Thus, the effects of ethanol are site- and time-dependent. This pattern differs from changes caused by chronic ethanol exposure, hence, neurotrophins must be vulnerable to the effects of withdrawal. Furthermore, the ethanol-induced changes do not appear to fit a model consistent with retrograde regulation, rather they suggest that neurotrophins act through autocrine/paracrine systems.

Prenatal alcohol exposure is known to cause damage to the central nervous system. This study sought to further elucidate the structural brain damage that occurs following prenatal alcohol exposure in both children and rats. Two children with histories of maternal alcohol abuse but who did not qualify for a diagnosis of Fetal Alcohol Syndrome (FAS), based on established criteria, underwent magnetic resonance imaging. Reduced volumes were found for the cerebrum and cerebellum. In addition, the proportional volume of the basal ganglia was reduced, although the proportional volumes of cortical and subcortical fluid, cortical gray matter, limbic and nonlimbic cortex, and diencephalic structures were unaffected. These findings are compared with our recent MRI findings in two cases of FAS. In addition, the caudate-putamen and ventricular areas were assessed in rats exposed to alcohol prenatally. Whereas the overall brain section area was not reduced in size, the area of the caudate-putamen was reduced and that of the ventricles was enlarged.

Patients with pure autonomic failure (PAF) and multiple system atrophy (MSA) may complain of feeling light-headed after alcohol ingestion particularly on assumption of the upright posture. The reasons for this have not been investigated. We therefore studied the effects of oral alcohol (40% vodka in sugar-free orange juice) and placebo (juice only) on the systemic and regional (including superior mesenteric artery, SMA) blood flow in nine patients with PAF and six patients with MSA. After alcohol, there was a fall in supine blood pressure (BP) and vasodilatation in the SMA but no change in cardiac output, or forearm muscle and cutaneous blood flow in either PAF or MSA; BP fell further during head-up tilt with no changes in levels of plasma catecholamines. After placebo, there were no changes while supine. We conclude that alcohol lowers supine BP and dilates the SMA with no change in muscle or cutaneous blood flow. Alcohol also enhances the fall in BP during head-up tilt. This may explain the symptoms experienced by PAF and MSA patients after alcohol.

AbstractParavertebral block is commonly used in the treatment for acute and chronic pain. The duration of paravertebral block could theoretically be prolonged with neurolytic agents. We report two cases of ultrasound‐guided neurolytic paravertebral blocks in patients suffering from intense cancer‐related thoracic pain. Ultrasound was used to identify the space and plane of injection at the mid‐thoracic level. Absolute alcohol was used to block the nerves at different segments. The two patients had great pain relief. Neurolytic paravertebral block can be a useful technique in patients with intractable cancer pain. Because of the risk of complication, it is recommended that this technique should be limited to relief of intractable pain in cancer patients with a poor prognosis.

Abstract Brain adenosine triphosphatase (ATPase) activity was examined in rats receiving varying doses of alcohol by inhalation of ethanol vapor for 7 days. Increased (Na+ + K+)-dependent ATPase activity was observed in the microsomes and, to a lesser extent, in the crude mitochondrial fraction. Gradient centrifugation of the crude mitochondrial preparation showed, however, that the increase in (Na+ + K+)-ATPase activity was in the synaptosomes. Increased (Na+ + K+)-dependent activity could be correlated with alcohol dose, while (Mg2+)-dependent ATPase activity was not altered significantly by the alcohol inhalation treatment. The synaptosomal uptake of 4 putative neurotransmitters was also examined in brain homogenates from rats receiving the highest dose of ethanol through inhalation. Despite a 30–40% increase in (Na+ + K+)-ATPase activity, transmitter uptake was not enhanced. Of the putative neurotransmitters studied, the transport of norepinephrine, 5-hydroxytryptamine and GABA did not change while the uptake of glutamate decreased by 16%.

Since serotonin (5-HT) reportedly is involved in aberrant drinking of ethyl alcohol, the present study examined a possible role of the concentration of 5-HT in systems originating in the dorsal raphe nucleus (DRN), median raphe nucleus (MRN) or both nuclei. The preference for alcohol offered in concentrations increased over 10 days from 3% to 30% was determined for each Sprague-Dawley rat. After the rats were anesthetized with sodium pentobarbital, either 10 microg 5,7-DHT or artificial cerebrospinal fluid (CSF) was micro-injected stereotaxically into the DRN, MRN or both nuclei. After 10 days, a second alcohol preference test was offered to the animals. Then the rats were decapitated, each brain removed, and the block of tissue containing injection sites was saved for histological analysis. The remaining portion was dissected into separate regions for analysis by HPLC of 5-HT, 5-hydroxyindoleacetic-acid (5-HIAA), norepinephrine (NE), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). The 5,7-DHT lesion of the DRN depleted the levels of 5-HT and 5-HIAA by 50-55% in the midbrain and pons and by 70-80% in the frontal cortex, whereas, the 5,7-DHT lesion of MRN reduced 5-HT in all regions except the corpus striatum. The depletion of 5-HT was lower in MRN-lesioned than in DRN-lesioned rats in the frontal cortex and nucleus accumbens. The combined lesion of both DRN and MRN produced a massive decline of >90% of 5-HT and 5-HIAA in all structures except the pons where 5-HT was reduced by 70%. Whereas the level of NE was reduced mainly in the frontal cortex, the levels of DA and its metabolites were essentially unaffected by the 5,7-DHT lesions. Although single or combined lesions of the DRN and MRN failed to alter the intake of alcohol of the rats, the combined serotonergic lesions increased significantly the ingestion of water but not food. Correlational analyses in the sham groups showed a negative association between the intake of alcohol and cortical dopamine and possible hippocampal 5-HT and NE as well as between the ingestion of food and of 5-HT in the frontal cortex. Taken together, these observations in the Sprague-Dawley rat suggest that lower levels of these monoamines in certain regions of the brain may play a role in the maintenance of the basal intake of alcohol but not in the drinking after the injection of 5,7-DHT. Explanations of our findings include: (1) a compensatory neurochemical change in pre- or postsynaptic 5-HT receptors subsequent to the dysfunction of serotonergic neurons in the forebrain; (2) a unique characteristic of the Sprague-Dawley strain of rat; and (3) residual quanta of 5-HT which sustains the pattern of alcohol drinking.

AbstractIn mammalian brain peripheral benzodiazepine (PBZD) receptors are predominantly localized on astroglial cells. Previous studies utilizing whole membrane preparations from brain and peripheral organs of various species have indicated several distinctions between the drug‐receptor interactions of the two prototypic PBZD receptor ligands, PK 11195 and Ro5‐4864. The present study was undertaken to determine whether putative differences in the binding of PBZD receptor ligands in homogenates of primary astrocyte cultures can be interpreted as the labeling of PBZD receptor subtypes. Equilib‐rium competition and saturation binding experiments in homogenate preparations of primary astrocytes from cerebral cortex of new born rats revealed that [3H]PK 11195 labels twice the number of [3H]Ro5‐4864 binding sites. Unlabeled Ro5‐4864 competes for [3H]PK 11195 binding in a manner suggesting the existence of multiple PK 11195 bind‐ing sites. The competition binding experiments, using various benzodiazepines, indicate that one binding component of PK 11195 corresponds to Ro5‐4864 binding sites, whereas the second is different. The latter binding site does not correspond to the central BZD receptor but displays the pharmacological properties of the PBZD receptor. Further differences between the binding of PK 11195 and Ro5‐4864 in astrocytes were detected in the presence of ethanol which was more effective in inhibiting the binding of the latter. Subcellular distribution studies indicated, however, that the binding of both [3H]PK 11195 and [3H]Ro5‐4864 is associated primarily with the mitochondrial fraction of astro‐cytes. Taken together, the present study indicates the existence of non‐overlapping PBZD binding sites in astrocytes and thus suggests the existence of PBZD receptor subtypes. It appears, however, that there is no distinction in the subcellular localization of the putative subtypes of the PBZD receptor. © 1993 Wiley‐Liss, Inc.

We examined the effect of chronic prenatal alcohol exposure (PAE) on the process of adult neurogenesis in C57BL/6J mice at early adulthood (PND 56). Pregnant mice, and their in utero litters, were exposed to alcohol, through oral gavage, on gestational days 7-16, with recorded blood alcohol concentrations averaging 184 mg/dL (CA group). Two control groups, sucrose (CAc) and non-treated (NTc) control groups were also examined. The brains of pups at PND 56 from each experimental group were sectioned in a sagittal plane, and stained for Nissl substance with cresyl violet, and immunostained for Ki-67 which labels proliferative cells and doublecortin (DCX) for immature neurons. Morphologically, the neurogenic pattern was identical in all three groups studied. Populations of Ki-67 immunopositive cells in the dentate gyrus were not statistically significantly different between the experimental groups and there were no differences between the sexes. Thus, the PAE in this study does not appear to have a strong effect on the proliferative process in the adult hippocampus. In contrast, the numbers of immature neurons, labeled with DCX, was statistically significantly lower in the prenatal alcohol exposed mice compared with the two control groups. Alcohol significantly lowered the number of DCX hippocampal cells in the male mice, but not in the female mice. This indicates that the PAE appears to lower the rate of conversion of proliferative cells to immature neurons and this effect of alcohol is sexually dimorphic. This lowered number of immature neurons in the hippocampus appears to mirror hippocampal dysfunctions observed in FASD children.