Effects of chronic ethanol and benzodiazepine treatment and withdrawal on corticotropin-releasing factor neural systems.
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Alcoholism↗
Biomedical subjects
C L Ehlers
Publications and source records attributed to C L Ehlers.
Long latency event related potentials in rats: the effects of changes in stimulus parameters and neurochemical lesions.
Animal models of event related potentials (ERPs) have recently been developed in order to gain further understanding of the psychobiological variables which may underlie these brain potentials. In the present study, unanaesthetized rats were utilized in order to evaluate the effects on rat ERP morphology of changes in the auditory stimulus parameters used to elicit these potentials such as tone probability and intensity. In addition, the consequences of reductions in norepinephrine (NE) produced by six-hydroxydopamine (6-OHDA) lesions to the area of the dorsal noradrenergic bundle in ERP wave forms were evaluated. Forty, experimentally naive, male rats chronically implanted with electrodes were used in this study. The results of these studies showed that in all electrode sites (frontal cortex, ventral thalamus, dorsal hippocampus, locus coeruleus) a series of large amplitude potentials in the 10-200 msec latency range could be recorded, some of which were sensitive to changes in the auditory stimulus parameters such as probability and tone intensity. Late positive potentials in the 300-400 msec range could be identified in recordings from the dorsal hippocampus and were found to be sensitive to probability independent of tone intensity. Dorsal noradrenergic bundle lesions were also found to produce significant changes in these rat ERP components. Lesioned animals were found to have increases in amplitude to the early negative potentials (in the 50-100 msec range) in response to frequent tones in cortical leads and decreases in the amplitude of the late positive potentials (in the 300-400 msec range) recorded in hippocampal leads in response to infrequent tones. These findings are consistent with a role for NE in the forebrain in the processing of novel or "selective" stimuli.
Animals↗
Corticotropin releasing factor (CRF): studies in alcohol preferring and non-preferring rats.
Electroencephalographic (EEG) responses to corticotropin releasing factor (CRF) as well as CRF concentrations in several brain regions were measured in two lines of rats which have been genetically selected for alcohol preferring (P) or non-preferring (NP) behaviors. Fifteen rats were implanted with chronic electrodes and EEG spectra were evaluated following intracerebroventricular (ICV) administration of CRF (0.15 nmol) or saline. P rats demonstrated a significantly increased EEG response to CRF in the theta frequency range (ANOVA: PREF x DRUG 4-6 Hz, P less than 0.03; 6-8 Hz, P less than 0.05) in frontal cortex. A significantly lower concentration of CRF was found in the P rats in hypothalamus (P less than 0.02), amygdala (P less than 0.003), prefrontal cortex (P less than 0.01), and cingulate cortex (P less than 0.02). The finding that P rats had an increased response to exogenously administered CRF, taken together with decreased CRF concentrations, suggests that CRF receptors may be up-regulated in these animals. Differences in the regulation of CRF neurons may contribute to the expression of behavioral preference for ethanol consumption in these rat lines.
Alcohol Drinking↗
Effects of dizocilpine (MK-801) and ethanol on the EEG and event-related potentials (ERPS) in rats.
Recent neurophysiological data have suggested an interaction of ethanol (EtOH) with the glutamate-NMDA receptor complex. For instance, low levels of alcohol have been found to inhibit the ion current, activated by NMDA in in vitro preparations. The present study extends these paradigms in order to evaluate the electrophysiological effects of ethanol and the nonspecific NMDA receptor antagonist, dizocilpine (MK-801) in awake, conscious rats. Twenty Wistar rats were stereotaxically implanted with electrodes, aimed at dorsal hippocampus, amygdala, thalamus and frontal cortex. Rats received the following drugs: saline (s.c.), 0.01 and 0.1 mg/kg MK-801 (s.c.); EtOH, 0.75 g/kg (i.p.); 0.75 kg EtOH plus 0.01 mg/kg MK-801; 0.75 g/kg EtOH plus 0.10 mg/kg MK-801. Five minutes of EEG was collected and event-related potentials (ERPs) recorded in response to an auditory "oddball" paradigm. Spectral analysis revealed that MK-801 (0.1 m/kg) produced significant increases in low frequency EEG components, at all sites (1-6 Hz) and decreases in higher frequencies (16-32 Hz). Whereas ethanol (0.75 g/kg) produced decreases in power in all frequency bands. The combined administration of EtOH and MK-801 produced some antagonistic effects on the EEG in the low frequency range. Evaluation of ERPs revealed that MK-801 (0.1 mg/kg) produced significant decreases in amplitude of the N1 and P2 components in the cortex, decreases in the P1 and N2 in the thalamus and a profound decrease in the P3 components in hippocampus and amygdala. Ethanol was also found to produce decreases in the N1 component in cortex. The administration of MK-801 and ethanol together did not produce significant interactions on ERPs. These studies suggest that antagonism of the NMDA receptor by MK-801 may produce some effects similar to those of ethanol, however, their combined administration did not produce synergistic effects within these dose ranges.
Amygdala↗
Electroencephalographic sleep studies in depressed outpatients treated with interpersonal psychotherapy: I. Baseline studies in responders and nonresponders.
Electroencephalographic (EEG) sleep measures have been examined as predictors of therapeutic response in patients with major depression. Although some studies have reported that EEG sleep measures are predictive of a favorable outcome with medications, two recent studies found no differences in the baseline sleep characteristics of responders and nonresponders to psychotherapy. To clarify this issue, we compared baseline EEG sleep in a group of patients with recurrent depression who responded to interpersonal psychotherapy (n = 19) and a comparable group who did not respond (n = 18). Baseline ratings of depression severity did not differ in the groups, but some differences in baseline sleep were noted. Psychotherapy nonresponders had longer sleep latencies, lower sleep efficiency, and increased automated measures of phasic rapid eye movement (REM) activity. In addition, the two groups had different EEG sleep adaptation patterns for REM latency and phasic REM density measures across the two study nights. These preliminary results suggest that baseline EEG sleep patterns, as well as the pattern of laboratory adaptation, may differ for depressed patients who respond to psychotherapy and those who do not.
Adolescent↗
Effects of chronic corticosterone treatment on electrophysiological and behavioral measures in the rat.
The electrophysiological and behavioral effects of daily oral exposure to a corticosterone or vehicle solution was evaluated in 20 male Wistar rats over a 10-wk period. Evaluation of the rats' behavior in an open field apparatus, as well as in automated locomotor cages, revealed no significant differences between steroid-treated and control animals following 5-6 wk of exposure. No differences in mean EEG power, as estimated by spectral analysis of cortical and dorsal hippocampal recordings, were observed between the two groups following 8 wk of exposure. However, some increases in EEG "stability" were noted in the corticosterone-treated rats. At 9 wk, responses to auditory stimuli, as assessed by evoked responses, in cortex and dorsal hippocampus were also found to be unaltered by corticosterone exposure. These studies suggest that exposure to daily oral corticosterone, in the doses used, over a period of 2-3 mo is not associated with gross electrophysiological or spontaneous behavioral effects in the brain areas assessed.
Animals↗
The effect of SRIF on the EEG sleep of normal men.
The aim of this investigation was to evaluate EEG sleep, especially measures of delta-wave sleep, during and after the administration of somatostatin (SRIF). Eleven normal men, ages 22-37 yr, were administered saline or SRIF (0.1 microgram/kg/min IV) over 160 min at bedtime. SRIF delayed sleep-related growth hormone (GH) secretion without altering the amount of GH available during the entire night of sleep. No changes in delta-wave sleep occurred during either the first 100 min of sleep or the remainder of the night. Furthermore, all major EEG sleep variables were not significantly different between the saline and SRIF infusion night. It would not appear that the peripheral administration of this dose of SRIF or the subsequent delay of GH release has quantitative effects on EEG measures of all-night sleep.
Adult↗
Social zeitgebers, biological rhythms and depression.
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Depressive Disorder↗
Subjective feelings of alcohol intoxication in Asians with genetic variations of ALDH2 alleles.
Asian-American men who possess ALDH2*2 alleles and who experience a facial flush after consuming alcohol were carefully matched on drinking history and demographic variables with nonflushing Asian males with only ALDH2*1 alleles. Each man was tested following placebo and a challenge dose of 0.75 ml/kg alcohol. Following alcohol, flushers reported experiencing significantly more positive feelings of intoxication than nonflushers, despite equivalent blood alcohol concentrations. These data suggest that Asians who flush after drinking, particularly those with ALDH2*1/2*2 genotype, have a more intense, although not necessarily a more negative, response to alcohol than comparable nonflushing Asians. This alcohol sensitivity reaction that many Asian flushers experience may contribute to their lower tendency to drink excessively, even though their response to alcohol is not predominantly negative.
Adult↗
Fetal alcohol syndrome: a case report of neuropsychological, MRI and EEG assessment of two children.
Neuropsychological, neuroanatomical, and electrophysiological data are presented on two subjects with fetal alcohol syndrome (FAS). Both boys had intelligence quotients in the mentally deficient range and were found to have several other severe, specific deficits. Magnetic resonance imaging showed abnormalities of the corpus callosum, and reductions in the size of the basal ganglia and thalamic structures. No focal abnormalities were noted in the electroencephalogram records, although the electroencephalograms of both boys were moderately abnormal for their age group. A multidisciplinary approach to the study of FAS, hopefully will lead to a more unified concept of the disorder and perhaps indicate specific areas of vulnerability.
Adolescent↗
EEG sleep profiles and recurrent depression.
Earlier investigations have suggested that electroencephalographic (EEG) sleep may be altered as a function of the duration of an episode of depression. We compared the EEG sleep profiles in a group of recurrent depressives who had been depressed for less than 6 weeks with their sleep profiles as measured during their previous episode of depression. Findings in this sample of 32 patients point to the presence of specific rapid eye movement (REM) sleep abnormalities as being more pronounced earlier in the course of a depressive episode. Changes in REM latency and REM activity were also reflected in reductions in EEG spectral power in almost all bandwidths during the first REM period of the recurrent episode. These results are not easily explainable on the basis of traditional measures of clinical severity or the number of episodes.
Adult↗
EEG and ERP response to chronic ethanol exposure in rats.
Chronic ethanol exposure has been described in humans to produce a series of long and short term electrophysiological consequences. Interpretation of the electrophysiological findings in human subjects, however, is made difficult due to concomitant factors, such as nutritional status, premorbid functioning and differences in genetic susceptibility to the effects of ethanol. In the present study, electroencephalograms (EEGs) and auditory event related potentials (ERPs) were utilized to explore the short and longer term effects of chronic ethanol exposure in rats. Rats were continuously exposed to ethanol vapors for a period for 1 month. This treatment produced a mean blood ethanol level of 178 +/- 13.86 mg%. EEGs and ERPs were subsequently collected at 10 min, 24 h, and 2 weeks following termination of ethanol exposure. Significant changes in the EEGs and ERPs of these rats could be demonstrated. EEG amplitude increases, as quantified by spectral analysis, were most prominent at the 24 h time period, perhaps reflecting a state of "rebound excitability". EEG responses were normalized in ethanol-treated rats by 2 weeks post-withdrawal. In contrast, reductions in the N1 and P2 amplitudes of the rat ERPs were prominent after chronic ethanol exposure and following 2 weeks withdrawal, suggesting that ethanol may produce some longer term effects on response to ERP stimuli. Taken together, these studies suggest that ethanol may produce differential effects on EEG and ERPs and that this model may provide a useful substrate for the evaluation of the mechanisms underlying the effects of chronic ethanol exposure.
Acoustic Stimulation↗
Combined effects of ethanol and MK 801 on locomotor activity in the rat.
The present study examined the effects of ethanol (0.75 g/kg IP) alone and in combination with the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist MK 801 (0.1 mg/kg SC) on the locomotor activity of rats. Sixteen rats were treated with vehicle plus saline, MK 801 plus saline, vehicle plus ethanol, and MK 801 plus ethanol. Locomotor activity was quantified for a period of 12 hours following drug administration. Ethanol was found to significantly decrease locomotor activity whereas MK 801 significantly increased locomotion during the first 2 hours postdrug. In addition, there was a significant additive interaction between ethanol and MK 801 during this time period. Two to four hours postdrug, MK 801 was observed to significantly decrease locomotion. Four to six hours postdrug, ethanol-treated rats had significantly increased locomotor activity whereas MK 801-treated rats displayed significantly decreased locomotion. No significant interaction was found between ethanol and MK 801 4 to 6 hours postdrug. No significant effects of any of the drugs on locomotor activity were observed from 6 to 12 hours postdrug. These results suggest that ethanol and MK 801 produce a pattern of effects on locomotor activity which depend on the time elapsed following drug administration.
Animals↗
Long latency event-related potentials in rats: effects of dopaminergic and serotonergic depletions.
The effects of serotonergic and dopaminergic depletions on event-related potentials (ERPs) generated by an auditory "oddball" paradigm were evaluated. Eighteen rats received either sham or six-hydroxydopamine (6-OHDA) lesions to the ventral tegmental area (VTA), and were subsequently implanted with electrodes in the frontal cortex, dorsal hippocampus (DHPC), and amygdala (AMYG). In these animals, a series of large amplitude potentials in the 10-200 ms latency range could be recorded from all the brain areas tested. In addition, late positivities (in the 300-400 ms range) were identified in DHPC and AMYG. 6-OHDA lesions to the VTA were found to produce a 30-46% reduction in dopamine, but did not significantly alter any of the ERP components. A second series of rats were implanted with electrodes in cortex and DHPC. These rats then received vehicle injections and subsequently injections of parachlorophenylalanine (PCPA). PCPA produced a 50% depletion of serotonin concomitant with significant reductions in the negative components in the 50-100 ms range recorded in hippocampus and cortex. These studies support a role for serotonin but not dopamine in the processing of passively presented auditory stimuli and further suggest that the rat may be a good model for the exploration of long latency ERPs.
Amygdala↗
Electrophysiological response to ethanol in P and NP rats.
Event-related potentials (ERPs) have been successfully used in human subjects to evaluate alcoholics as well as those at risk for the future development of alcoholism. In the present study, two lines of rats, those with a preference for ethanol consumption (P) and those not preferring (NP) to drink ethanol were studied using ERP-producing stimuli. Rats were implanted with electrodes in the frontal cortex and dorsal hippocampus (DHPC). A passive auditory "oddball" paradigm was used to record ERP responses following saline and two doses (0.5, 1.0 g/kg) of ethanol. P and NP rats differed under the saline condition in that P rats had smaller N1-like ERP components and larger P2 waves in both cortex and hippocampus. P and NP rats were also found to differ in response to ethanol administration. NP rats evidenced dose-dependent reductions in ERP component amplitudes such as the N1 recorded from cortical sites. P rats did not have such reductions in N1 amplitudes and in fact, displayed increased N1 amplitudes in hippocampal sites. These studies provide further electrophysiological evidence that rats with a genetically influenced preference for ethanol consumption differ from nonpreferring rats at baseline and have a less intense depressant or more stimulating response to ethanol challenge.
Alcohol Drinking↗
The effect of GRF on the EEG sleep of normal males.
The administration of GRF in young men either before sleep onset or coinciding with sleep onset leads to an immediate significant increase in GH secretion. These increases were not associated with major alterations in sleep including slow-wave sleep.
Adult↗
Nonlinear analysis of EEG sleep states.
Recent advances in the field of nonlinear dynamics have provided new conceptual models as well as novel analytical techniques applicable to neuropsychopharmacologic studies. One measurement technique that has been recently developed in an attempt to characterize nonlinear systems in physics and biology is the estimation of dimension. Dimension may be seen as a measure of the information required to describe the current behavior of a system. We have applied these techniques to the analysis of the sleep EEG, and have found that the dimension of rapid eye movement (REM) sleep is significantly higher than non-rapid-eye-movement (NREM) sleep. These data support a preliminary hypothesis that EEG dimension may represent the number of nonlinear modes activated in the brain. Thus, sleep states of low arousal or low input would be envisioned as having low dimension (e.g., slow-wave sleep) whereas increased arousal (REM) would activate more nonlinear modes. Although more investigations will be needed to explore this hypothesis, these studies suggest that further development of nonlinear approaches to the analysis of brain systems are likely to generate new clinical measures as well as new ways of viewing brain electrical function.
Adult↗
Evaluation of EEG alpha activity in sons of alcoholics.
The results of computer-analyzed electroencephalographic (EEG) data from 24 sons of alcoholics (family history positive [FHP]) and their matched controls (family history negative [FHN]) were compared before and 90 minutes following alcohol and placebo challenge. Blind analysis of the data revealed that FHP men had more energy in the fast-frequency alpha range (9 to 12 Hz) of their EEG than did FHN subjects at baseline. EEG response to ethanol was also found to differ between the two groups. FHN but not FHP subjects evidenced a decrease in fast-frequency alpha energy following ethanol challenge. These data support other evidence of a less intense reaction to ethanol in FHPs as measured by subjective response, body sway, and hormone levels. In addition, these findings suggest that certain normal alpha wave variants may be more common in sons of alcoholics.
Adult↗