Biomedical subjects

D J Knapp

Publications and source records attributed to D J Knapp.

35 records · Page 2Linked to original sources

PubMed1997

Flumazenil blockade of anxiety following ethanol withdrawal in rats.

In previous research, the drug flumazenil has been categorized both as a pure benzodiazepine antagonist and as a benzodiazepine partial agonist. The following studies used an elevated plus maze to test whether flumazenil would exert any antianxiety action in rats. While chlordiazepoxide (3.0 mg/kg), ethanol (0.75 g/kg), and the atypical benzodiazepine zolpidem (1.0 mg/kg) all significantly increased time spent on the open arms and percent open arm entries, flumazenil (1-10 mg/kg) alone did not produce any anxiolytic effects on the maze. Withdrawal from chronic ethanol treatment led to a decrease in open arm time and percent open arm entries. Flumazenil (3.0 mg/kg) blocked these changes, suggesting that the effects of flumaxenil are at least partially dependent upon the levels of stress or anxiety in the subjects. An anxiolytic action of flumazenil was not seen following the central administration of the neuropeptide corticotropin-releasing factor (CRF), which reduced open arm time on the elevated plus maze. These results support the hypothesis that the mechanism of action for flumazenil effects on the anxiety observed during ethanol withdrawal involves antagonism of an endogenous benzodiazepine inverse agonist, rather than activity as a partial agonist or blockade of CRF-mediated effects.

Animals↗

PubMed1997

Behavioral similarities and differences among alcohol-preferring and -nonpreferring rats: confirmation by factor analysis and extension to additional groups.

Thirteen behavioral variables from six tasks were measured in alcohol-preferring (AA, FH, and P) and -nonpreferring (ANA, FRL, and NP) rat lines/strains and subjected to Factor Analysis. Four Independent factors accounted for > 90% of the variance. Defecation in the open field and ultrasonic vocalizations after an air puff were negatively correlated with alcohol intake and preference, whereas the increase in daily fluid intake in the presence of saccharin was positively correlated. Other factors could be labeled Activity, Emotionality, and immobility Factors, and each was independent of the Alcohol Factor. When an additional alcohol-preferring rat line (HAD) and two additional nonpreferring groups (LAD and ACI) were tested, they were found to differ on most behaviors that were associated with alcohol intake and preference in the Factor Analysis; vocalizations and saccharin-induced increase in fluid intake, but not defection. A new Factor Analysis was then performed incorporating these three new groups and including five new behavioral measures. The following measures had high loadings on the Alcohol Factor: alcohol intake under choice conditions; alcohol preference; forced alcohol intake; alcohol acceptance (forced alcohol intake/basal water intake x 100); ultrasonic vocalization; saccharin intake; saccharin-induced increase in daily fluid intake; defecation in the open field test; and immobility in a modified forced swim test. These findings indicate that there are indeed certain behavioral characteristics that are common among alcohol-preferring rat lines/strains, but there are also substantial group differences on other behavioral measures. For those behavioral measures reflecting emotionality (defecation and ultrasonic vocalization) that loaded highly on the Alcohol Factor, the alcohol-preferring rats had lower scores.

Alcohol Drinking↗

PubMed1997

Ultrasonic vocalization behavior differs between lines of ethanol-preferring and nonpreferring rats.

To further understand the relationship between emotional state and alcohol intake in rats, the tendency to emit ultrasonic vocalizations in response to an aversive, but nonpainful, air puff stimulus was tested in several rat lines. Included in this group were Maudsley Reactive (MR) and Non-Reactive (MNR) rats, and several lines of rats with either high ethanol preference or a low ethanol preference: Preferring, (P), Alko-Alcohol (AA), and Fawn-Hooded (FH) animals; and Non-Preferring (NP), Alko-Non-Alcohol (ANA), and Flinders Resistant Line (FRL). MR rats emitted fewer ultrasonic vocalizations (USVs) and showed less preference for ethanol than did MNR animals. An overall analysis that included the P, NP, FH, FRL, AA, and ANA groups demonstrated a significant negative correlation between the total number of USVs emitted and ethanol consumption. NP, FRL, and especially ANA rats (low ethanol-preferring) emitted the most USVs--to an extent similar to that typically found for normal rats. The duration of vocalizing was higher only in the NP and the FRL rats the relative to their P and FH comparison groups, respectively. In the ethanol-preferring and nonpreferring lines, the numbers of USVs emitted correlated positively with the duration of vocalizing, but not with the latency to vocalize, which in turn did not correlate strongly with ethanol intake. The latency to vocalize did not correlate significantly with ethanol intake across all drinking lines or MR or MNR rats, but was found to be higher in FH and AA rats relative to their nondrinking comparison groups. These associations suggest that the relationship between emotional state and ethanol drinking is complex and cannot be attributed to a simple elevated state of anxiety or emotionality. Further examination of the central nervous system mechanisms mediating the difference in USVs between paired lines of ethanol-preferring and nonpreferring rats may identify neurochemical factors that predict ethanol preference.

Alcohol Drinking↗

PubMed1996

Neuroanatomical characterization of Fos induction in rat behavioral models of anxiety.

Immunohistochemical staining for Fos-like immunoreactivity (Fos-LI) was used to map functional activation in discrete brain regions of rats processed in three empirical models of anxiety: foot shock avoidance responding in a shuttle box, the elevated plus maze, and an air puff-induced ultrasonic vocalization test. The avoidance test and elevated plus maze induced prominent Fos-LI in select brain regions, including the medial prefrontal, cingulate, and ventrolateral orbital cortices, taenia tecta, nucleus accumbens, paraventricular nucleus of the hypothalamus, medial nucleus of the amygdala and lateral septum. Air puff stimuli that produced ultrasonic vocalizations induced Fos-LI to a more limited extent compared to the plus maze and avoidance test, with only the medial prefrontal cortex, medial nucleus of the amygdala, and lateral septum being significantly affected by air-puff. Even though the sensory stimuli and environmental conditions associated with the three anxiety models were markedly different, specific common forebrain regions were affected, i.e. the medial prefrontal cortex, medial amygdala, and lateral septum. It is hypothesized that these regions are components of a circuit in the rat brain related to anxiety or distress. To determine the potential relationship between generalized arousal and the observed induction of Fos-LI in the anxiety models, rats were tested in a non-aversive situation involving marked behavioral activation. Accordingly, after vigorous bar pressing behavior for reinforcement with sweetened condensed milk, induction of Fos-LI was minimal and comparable to that in unhandled control rats. These latter data indicate that the distinctive neuroanatomical patterns of Fos-LI observed in the paradigms related to anxiety were not simply due to generalized behavioral activation. In summary, select common brain regions were identified that express Fos-LI in empirical models of anxiety. These data provide a functional framework to explore neuroanatomical sites of action of psychotherapeutic drugs that influence behavioral responses in these tasks.

Animals↗

PubMed1996

Further selection of rat lines differing in 5-HT-1A receptor sensitivity: behavioral and functional correlates.

It was previously reported that selection for differences in the hypothermic effects to the selective 5-HT-1A agonist, 8-OH-DPAT, occurred rapidly, with very substantial differences present by the fourth generation. The present communication summarizes the findings from the next five generations of selection and from behavioral and other functional studies on these rats. The rats which were more sensitive to 8-OH-DPAT (High DPAT Sensitive-HDS) exhibited decreases in temperature of 4 degrees C or more and the distribution did not overlap with that of the rats which were less sensitive to 8-OH-DPAT (Low DPAT Sensitive-LDS) which exhibited decreases in temperature of 1.5 degrees C or less. The randomly bred control group (Random DPAT Sensitive-RDS) exhibited intermediate temperature decreases (means of 1.6-1.8 degrees C), with time overlap with the distributions of the selected groups. Pretreatment with pindolol, a 5-HT-1A antagonist, reduced the hypothermic response to 8-OH-DPAT, but pretreatment with ritanserin, a 5-HT-7 and 5-HT-2A/C antagonist, had no effect, confirming that the hypothermic response to 8-OH-DPAT is mediated predominantly by 5-HT-1A receptors. The HDS rats were less mobile in a forced swim test and drank more saccharin solution in a two-bottle choice paradigm than the LDS or RDS rats over several generations. In contrast, there were no consistent differences among the groups for open field activity or performance in an elevated plus maze. There were no differences among the groups for voluntary alcohol intake, but the HDS rats exhibited greater suppression of alcohol and saccharin intake after injection of 8-OH-DPAT (0.125 mg kg-1). The HDS rats were also found to have a higher number of 5-HT-1A binding sites in cortical regions than the LDS or RDS rats, but there were no 5-HT-1A binding site differences in the raphe nuclei. These findings clearly show that consistent behavioral differences do occur in the 8-OH-DPAT-selected lines of rats, but only for behaviors related to possible depression or reward, not anxiety. The pattern of binding results suggests that these behavioral correlates of 8-OH-DPAT selection may be related to changes in cortical 5-HT-1A receptors rather than raphe autoreceptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1996

Functional classification of antidepressants based on antagonism of swim stress-induced fos-like immunoreactivity.

Autoradiographic analysis of 14C-2-deoxyglucose (2-DG) uptake and immunocytochemical assessment of Fos-like immunoreactivity (Fos-LI) were used to assess swim stress-induced changes in metabolic activity in brain and to define the effect of chronic treatment with antidepressants from different pharmacological classes. Saline-treated rats processed in the forced swim test exhibited marked increases in Fos-LI in limbic cortical regions, lateral septum, medial amygdala and paraventricular nucleus of the hypothalamus (PVN). Uptake of 2-DG was increased by swim stress in some of the same brain regions where Fos-LI was induced, with the notable exception of a lack of a change in the PVN. Rats received injections for 3 wk with imipramine, desipramine, fluoxetine, nisoxetine, tranylcypromine or mianserin before being processed in the forced swim test. Chronic treatment with imipramine and desipramine alone induced Fos-LI in the central nucleus of the amygdala and the dorsolateral bed nucleus of the stria terminalis. After tranylcypromine treatment, Fos-LI was induced in many brain regions including limbic cortex, amygdala and paraventricular nucleus of the hypothalamus. None of the other antidepressants induced Fos-LI in any brain region examined. Chronic administration of imipramine, desipramine and nisoxetine antagonized the swim induced expression of Fos-LI in the PVN and in limbic cortical regions, including the medial prefrontal ventrolateral orbital and cingulate cortices. Chronic treatment with fluoxetine, tranylcypromine and mianserin did not alter swim stress-induced Fos-LI in any brain region. Thus, only antidepressant drugs that affect norepinephrine uptake (i.e., imipramine, desipramine and nisoxetine) antagonized swim stress-induced Fos-LI. In contrast to the action of chronic imipramine on Fos-LI induced by swim, chronic administration of imipramine did not antagonize the stress-induced changes in 2-DG uptake in limbic cortical regions. Acute administration of propranolol, which blocks beta-adrenergic receptors, reduced the number of cells staining for Fos-LI in limbic cortical regions, resembling the effects produced by chronic imipramine, desipramine and nisoxetine. In the PVN, neither propranolol nor prazosin (an alpha 1 antagonist) blocked the swim-induced Fos-LI, suggesting that swim-induced Fos-LI in the PVN is not under control of beta- or alpha 1-adrenergic receptors. These latter results imply that adaptation of noradrenergic receptors by chronic imipramine may not be related to the antagonism of stress-induced Fos-LI. The clear functional differences of the various antidepressant agents on swim stress-induced Fos-LI after chronic administration provide a functional classification of antidepressant drug action not previously identified.

Animals↗

PubMed1996

Human carcinomas variably express the complement inhibitory proteins CD46 (membrane cofactor protein), CD55 (decay-accelerating factor), and CD59 (protectin).

Normal human tissues express membrane-associated complement inhibitory proteins that protect these tissues from damage by autologous complement. To determine whether neoplasms also express these proteins, we examined the distribution of the complement inhibitors decay-accelerating factor (DAF), CD59 (protectin), and membrane cofactor protein in frozen samples of human breast, colon, kidney, and lung carcinomas and in adjacent non-neoplastic tissues, using immunohistochemistry. All samples were also studied for deposition of C3 fragments and activated C5b-9. Differences between normal tissues and the corresponding neoplasms were often observed, with loss or gain of expression of one or more inhibitors. Ductal carcinomas of the breast showed the most variation in phenotype; some tumors expressed only one inhibitor while others expressed different combinations of two or three inhibitors. Colon carcinomas, by contrast, stained intensely for all inhibitors. Renal cell carcinomas had weak to moderate expression of one to three inhibitors, generally DAF and CD59, whereas non-small cell carcinomas of the lung usually expressed CD59 and membrane cofactor protein with variable DAF immunoreactivity. The two small cell carcinomas of the lung showed little or no staining for any inhibitor. Activated C5b-9 deposition was seen adjacent to tumor nests in a minority of carcinomas and showed no correlation with complement inhibitor expression. C3 fragment deposition was minimal. Our results demonstrate that most carcinomas, with the exception of small cell carcinomas of the lung, do express one or more complement inhibitors at a level likely to inhibit complement-mediated cellular damage. Unexpectedly, large quantities of DAF and CD59 were often observed in tumor stroma, with only limited deposition in normal connective tissue. This suggests that carcinomas may supplement the activity of membrane-associated complement inhibitors by release of soluble forms of DAF and CD59 into the surrounding extracellular matrix.

Antigens, CD↗

PubMed1995

An air-puff stimulus method for elicitation of ultrasonic vocalizations in rats.

Rat 22 kHz ultrasonic vocalizations (USVs) are thought to reflect an aversive behavioral state, perhaps a type of anxiety or fear, and have proven useful in the study of the neural mechanisms of these states. This paper describes a simple procedure for presentation of an aversive but non-painful air-puff stimulus for the elicitation of USVs from rats. When directed at the rat's dorsal or dorsolateral head and neck region, this stimulus reliably elicits ultrasonic vocalizations from nearly all rats tested and as such represents a valuable alternative to other stimuli such as aggressive encounters, electric shock, or acoustic startle. The USV response may attenuate with repeated testing, yet remains readily inducible and is therefore suitable for studies involving habituation. The materials for generating this stimulus and the accompanying testing procedure comprise an efficient method with which this aversively motivated rodent behavior can be examined. The potential utility of this technique in studies of aversively motivated behaviors and its relevance to studies of startle responding is discussed.

Animals↗

PubMed1995

Effect of zolpidem on gamma-aminobutyric acid (GABA)-induced inhibition predicts the interaction of ethanol with GABA on individual neurons in several rat brain regions.

Previous investigations have suggested a relationship between zolpidem binding within specific brain regions and the ability of ethanol or zolpidem to enhance gamma-aminobutyric acid (GABA)-induced inhibition. The purpose of the present study was to extend our electrophysiological analysis to additional brain sites with high levels of zolpidem binding. In the brain regions chosen, red nucleus and globus pallidus, GABA-induced inhibition was shown to be enhanced by either ethanol or zolpidem on some, but not all, neurons. These findings led to the hypothesis that the effect of zolpidem on GABA-induced inhibition would predict the action of ethanol on responses to GABA for that neuron. When zolpidem and ethanol were applied individually to the same neurons in the red nucleus and globus pallidus, those neurons sensitive to zolpidem enhancement of GABA also were sensitive to ethanol. Conversely, if zolpidem did not enhance responses to GABA, ethanol did not enhance responses to GABA at these brain sites. A similar relationship between the abilities of zolpidem and ethanol to enhance GABA-induced inhibition was obtained in 90% of the neurons studied in the medial septum/diagonal band and ventral pallidum. These studies provide further support for the contention that the zolpidem-sensitive GABAA-benzodiazepine isoreceptor also responds to ethanol. Finally, the expression of GABAA subunit mRNAs was analyzed by polymerase chain reaction from micropunches of several brain regions that contain zolpidem binding sites and exhibit sensitivity to ethanol. Polymerase chain reaction analysis proved more sensitive than in situ hybridization in the detection of receptor subunit mRNAs. Several subunits (alpha 1, alpha 2, alpha 3, beta 2, beta 3 and gamma 2) were common to all brain regions in which ethanol and zolpidem enhanced GABA responses. GABAA receptor alpha 4/5, alpha 6, beta 1, gamma 1, gamma 3 and delta subunits were not consistently expressed in association with the presence of zolpidem binding. These data are consistent with the view that one native GABAA receptor to which zolpidem binds, and on which ethanol acts, contains the GABAA receptor subunits alpha 1, beta 2 and gamma 2; however, the present investigation did not preclude the possibility that other subunit combinations can contribute to ethanol and zolpidem enhancement of responses to GABA.

Animals↗

PubMed1994

Effects of ethanol, MK-801, and chlordiazepoxide on locomotor activity in different rat lines: dissociation of locomotor stimulation from ethanol preference.

Several lines of research have suggested a link between the reward value of a drug and its ability to stimulate locomotion. One goal of the present study was to determine whether ethanol preferentially stimulates locomotor activity in lines of rat that show a preference for ethanol. A secondary goal was to determine the extent to which the benzodiazepine-like and NMDA antagonistic action of ethanol accounted for its effect on locomotor activity. To meet these goals, the effects of varying doses of ethanol (0.125-1.0 g/kg), MK-801 (0.1-0.3 mg/kg), and chlordiazepoxide (0.3-3 mg/kg) on locomotor activity were studied in several lines of rats that had been habituated to the testing procedure. The effect of low doses of ethanol on motor activity in the Alcohol-Preferring (P) and Fawn-Hooded rats, which show a strong ethanol preference, were similar to those of the alcohol-nonpreferring (NP), Flinders Sensitive Line, and Flinders Resistant Line rats. Only the Flinder Resistant Line rats showed a small, but significant increase in locomotor activity after the administration of ethanol. The highest dose of ethanol (1.0 g/kg) produced locomotor depression in all lines except the P and NP lines, which were not tested at this dose. These findings do not support a link between locomotor stimulation by ethanol and ethanol preference. In contrast, all lines exhibited locomotor stimulation after moderate (0.1-0.3 mg/kg) doses of MK-801, but did not exhibit increases in activity following any dose of chlordiazepoxide. These data indicate that the profiles of activity after MK-801 and chlordiazepoxide were distinct from that of ethanol in the various rat lines.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗

PubMed1994

Effects of ethanol, chlordiazepoxide, and MK-801 on performance in the elevated-plus maze and on locomotor activity.

The effects of ethanol, chlordiazepoxide, and MK-801 on performance in the elevated-plus maze and on activity measured in a circular activity monitor were compared in Sprague-Dawley rats to determine whether these effects of ethanol could be explained by its action on either GABAA or NMDA receptors. Both ethanol and chlordiazepoxide produced an increase in the time spent in the open arms of the elevated-plus maze and in the ratio of open arm to total arm entries, indicative of an anxiolytic action of these drugs. MK-801 did not alter either the time spent in the open arms or the ratio of open to total arm entries. Chlordiazepoxide and MK-801 produced an increase in total arm entries that suggested that these compounds were increasing locomotor activity. Ethanol also increased total arm entries, but the effect was not statistically reliable. Following habituation to an activity monitor, neither ethanol nor chlordiazepoxide increased activity in this task, whereas MK-801 produced a robust increase in locomotion. Additionally, neither ethanol nor chlordiazepoxide blocked the MK-801-induced locomotor stimulation. The latter finding suggests that the effects of ethanol on GABAA receptors was not blocking an increased activity level produced by its antagonism of NMDA. Additionally, these results indicate that the anxiolytic and locomotor action of ethanol in rats parallel the effects of a benzodiazepine and not those of an NMDA antagonist. Finally, these results suggest that the consequence of ethanol's antagonism of NMDA receptor function is more restricted than that produced by MK-801.

Animals↗

PubMed1994

Neuroanatomical specificity and dose dependence in the time course of imipramine-induced beta adrenergic receptor down-regulation in rat brain.

The time course of beta adrenergic receptor adaptation in response to chronic imipramine treatment (10 or 20 mg/kg) was assessed by quantitative autoradiographic analysis of 125I-pindolol binding in rat brain. Binding of the radioligand was assessed in 18 brain areas, including subregions of the hippocampus, amygdala, septum, hypothalamus and specific cerebral cortical regions. After only 2 days treatment with imipramine at a dose of 20 mg/kg, select cortical regions exhibited a reduction in 125I-pindolol binding. These rapidly adapting cortical regions included the medial prefrontal, lateral frontal, ventrolateral orbital and piriform cortices. After 7 or 21 days treatment with imipramine at 20 mg/kg, 16 of 18 brain regions examined exhibited significant reduction in 125I-pindolol binding. The only regions examined that did not show reduced 125I-pindolol binding for these treatment conditions were the caudate-putamen and anterior hypothalamic area. After 2 days treatment with 10 mg/kg of imipramine, down-regulation of beta adrenergic receptors was not observed in any region. After 7 days treatment with 10 mg/kg, down-regulation of beta adrenergic receptor binding was found only in certain cortical regions: medial prefrontal, lateral frontal, ventrolateral orbital and piriform cortices. Thus, the cortical regions that were most rapidly affected with the 20 mg/kg dose of imipramine (i.e., after 2 days) were also the first to respond with the 10 mg/kg dose of the drug. After 21 days treatment with imipramine at 10 mg/kg, 125I-pindolol binding was reduced in 13 of the 18 regions examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Ethanol prevents desensitization of 5-HT2 receptor-mediated responses consequent to defeat in territorial aggression.

The effect of intruder status in territorial aggression on behavior in the elevated plus-maze, the open field and on 5-HT2 receptor-mediated behaviors was evaluated in male Long-Evans hooded rats. Intruders (350 g) were placed in the home cages of aggressive resident rats (475-600 g) and removed after 20 roll-tumble fights. On the following day, the rats were tested on the elevated plus-maze, and behavior in the open field was evaluated after injection with the 5-HT2/1C receptor agonist, DOI (1.0 mg/kg). The number of headshakes following DOI injection are thought to be an indicator of 5-HT2 receptor function. Although several other stressors were evaluated, only defeat in territorial aggression caused a significant decrement in the number of headshakes following DOI injection. To determine if ethanol (ET) could decrease the behavioral consequences of defeat, the effect of ET (1.25 g/kg) given before and immediately after aggression on behavior 24 hours later was evaluated. Although ET treatment had no effect on the control group that did not experience aggression, the ET treatment attenuated the desensitization of 5-HT2 receptor-mediated responses induced by aggression and severely exacerbated the anxiety-like effects as measured in the elevated plus-maze. These data suggest that (1) 5-HT2 receptor sensitivity decreases as a consequence of defeat, but not after several other stressors; (2) defeat in territorial aggression results in significant anxiety-like effects in the elevated plus-maze 24 hours later; and (3) these anxiety-like effects are exacerbated when ET is given before, and immediately after, the aggression.(ABSTRACT TRUNCATED AT 250 WORDS)

Aggression↗

PubMed1993

Observations of novel behaviors as indices of ethanol withdrawal-induced anxiety.

One of the prominent symptoms in alcoholics during withdrawal is an intense feeling of anxiety. Recently new tests have become available which may index anxiety in rodents. We have evaluated two such tests in our model of withdrawal from ethanol (ET) in rats. Rats were given either ET in milk (7-13 g/kg/4 days) or equicaloric dextrin maltose in milk via implanted gastric cannuli. Rats were scored for classical withdrawal symptoms (tremors, convulsions, stereotyped behavior), for stimulus-elicited ultrasonic vocalizations (USVs), and in one study for exploration of novel objects placed in their home cage at various points after the last dose of ET. In Sprague-Dawley rats, classical withdrawal symptoms were highest between 8-12 hours, and disappeared by 36 hours. Latency to explore a novel object was unchanged, but duration was depressed between 10-30 hours, and was recovered by 70 hours. Following a less intense Day 1 treatment regimen in Long-Evans rats, the vocalizations were greatly increased in number, and peak response occurred sooner (6 hours post-infusion) and was of shorter overall duration (50 hours). Pretreatment with diazepam (1.25-5.0 mg/kg) depressed the number of vocalizations during ET withdrawal (ETW), which suggests that this measure could index anxiety in animal models of withdrawal from ET.

Animals↗

PubMed1992

Zacopride, a 5-HT3 receptor antagonist, reduces voluntary ethanol consumption in rats.

The effect of the selective 5-HT3 receptor antagonist, zacopride, was assessed in male Sprague-Dawley rats in free choice (6% ethanol and water) experiments. In Experiment 1, single zacopride (0.01-10 mg/kg, IP) injections failed to alter ethanol (ET) consumption during 1-h restricted ET access. In Experiment 2, zacopride (5.0 and 10 mg/kg, IP) injected twice daily for 5 days significantly reduced ET intake and ET preference during 24-h free access to 6% ET and water without altering the total volume of fluid consumed. Thus, the schedule of ET access (i.e., free vs. restricted) and/or the duration of drug treatment may determine the efficacy of pharmacological agents in altering ET preference. 5-HT3 receptor blockade may reduce serotonin/dopamine-mediated maintenance of ET preference; a process that may proceed via extinction mechanisms.

Animals↗

PubMedDate not supplied

Interaction of nutrition and binge ethanol treatment on brain damage and withdrawal.

To determine if nutrition plays a role in ethanol withdrawal and alcohol-induced brain damage, the effects of a 4-day ethanol binge treatment using ethanol in a nutritionally complete liquid diet compared to ethanol mixed with water were studied. The nutritionally complete diet group (ETOH-diet) received a complete diet of sugars, proteins and fats with vitamins and minerals with approximately 53% of calories from ethanol while the nutritionally deprived group (ETOH-H2O) received 100% of calories from ethanol. No difference in withdrawal behavior was found between the ETOH-diet and ETOH-H2O groups during the 72-hour period studied. In addition, no difference was seen for serum levels of magnesium and zinc taken at last dose or following 72 h of withdrawal. Serum alanine aminotransferase (ALT) and ammonia were increased in both groups with ETOH-diet showing a greater increase in ALT than ETOH-H2O. Both groups showed damage in the olfactory bulb, perirhinal, agranular insular, piriform and lateral entorhinal cortical areas as well as hippocampal dentate gyrus and CA-3. Interestingly, the ETOH-diet group displayed more damage at last dose in the posterior dentate and CA-3 of hippocampus than did the ETOH-H2O group. This study suggests that nutritional components and total caloric intake do not effect behavior during ethanol withdrawal and that a nutritionally complete diet may increase ethanol-induced brain damage.

Alanine Transaminase↗

PubMedDate not supplied

Chronic ethanol treatment of rats and the myocardial beta-adrenoceptors.

We examined the effect of chronic treatment with ethanol on the dynamics of beta-adrenoceptor binding in left ventricular myocardium of rats. After treatment with BAAM (20 mg/kg i.p.), an irreversible inhibitor of beta-adrenoceptors, the inhibition of beta-adrenoceptor binding was less, and the recovery of receptor binding was faster in chronically ethanol-treated rats compared to the control animals given equicaloric dextrin maltose treatment. When intracellular beta-adrenoceptor recycling was inhibited with colchicine, cytoplasmic left ventricular beta-adrenoceptor binding was greater in ethanol-treated compared to dextrin maltose-treated animals. We conclude that the previously reported decreased functional activity of the beta-adrenoceptor-mediated system probably reflects the contribution of ethanol-mediated effects not entirely restricted to the receptor-binding mechanisms.

Adrenergic beta-Antagonists↗