Characteristics of ethanol drinking patterns under schedule-induced polydipsia

Rats were induced to consume concentrations of ethanol between 5% and 10% (w/v) using the schedule-induced polydipsia technique. Although the substitution of ethanol solutions for water disrupted the usual post-pellet pattern of drinking, large amounts of ethanol were consumed and sound-induced convulsions were observed during ethanol withdrawal. In subsequent experiments, other rats chose 5% and sometimes 10% ethanol solutions over water where both water and ethanol were freely available during the first session of exposure to ethanol. Convulsions and wild running behavior could be observed in some of these rats after only 8 days of drinking, even though ethanol was freely available at all times. Use of the schedule-induced polydipsia technique served to bring the rats into early contact with the ethanol, but rats that received the same number of food pellets in a dish rather than by the schedule drank almost as much ethanol as did the rats receiving ethanol by the schedule. Rats with free access to food pellets drank very little ethanol.     

Evaluation of limited and unlimited food intake during withdrawal in triazolam-dependent baboons

Chronic administration of benzodiazepine (BZ) agonists in baboons typically increases food intake, in a dose-dependent manner, during drug administration and suppresses food intake after termination of drug dosing. To determine if suppressed food intake after termination of chronic BZ administration (i.e. withdrawal) was related to increased food consumption during drug administration, the effects of chronic triazolam (1.0 mg/kg/day, intragastrically, for 30-34 days) and subsequent triazolam withdrawal on food intake was studied under two conditions in each of four baboons: (1) when the number of pellets was unlimited; and (2) when the number of pellets was limited so that pellet intake could not increase above the mean number of pellets per day obtained during a preceding vehicle condition. Pellets were available during daily 20-h sessions under a fixed-ratio 10 schedule of reinforcement. All baboons completed both pellet conditions, and the order of exposure was counterbalanced across subjects. During the unlimited pellet condition, pellets per day were increased during triazolam administration and then were suppressed in a time-limited manner when triazolam was discontinued in all four baboons. When pellet intake was limited during triazolam administration, pellet intake after triazolam discontinuation was suppressed in three of four baboons, and the magnitude and duration of suppression was generally less than during the unlimited pellet condition. Other behavioral signs of withdrawal (e.g., tremor/jerk, vomit/retch) were observed in all four baboons under both pellet conditions. These data suggest that the hyperphagic effects of triazolam appear to contribute to the subsequent suppression of food intake during triazolam withdrawal. However, these hyperphagic effects do not account for the entire phenomenon of suppressed food intake during BZ withdrawal.     

Differential effects of two cannabinoid receptor agonists on progressive ratio responding for food and free-feeding in rats

The cannabinoid receptor agonists delta9-tetrahydrocannabinol (delta9-THC) and HU-210 were compared in terms of their effects on: (1) progressive ratio (PR) responding for food, and (2) free food intake. In the first experiment, food-deprived Wistar rats were trained on a time-constrained (60 min) PR-5 schedule for food reinforcement, in which the response requirement incremented by five lever presses for each successive reinforcer. One group of rats received vehicle, 0.5, 1 or 3 mg/kg delta9-THC (i.p.), and three other groups received HU-210 (i.p.) at three different dose ranges, spanning 0.001-0.1 mg/kg. In the second experiment, the effects of the two drugs on free food intake were tested in a separate group of non-deprived rats. For PR responding, delta9-THC significantly increased the break point (final ratio completed) and the total number of lever presses emitted. The same drug also significantly increased free food intake. However, the effects of HU-210 were quite different: it did not alter PR responding at any dose; instead, its only significant effect was to reduce free food intake at 0.06 mg/kg. These data suggest that increased motivation to obtain food might underlie the hyperphagic effects of delta9-THC. However, the synthetic agonist HU-210 has different effects: it only acts to reduce feeding behaviour, an outcome that probably reflects non-specific behavioural disruption. These findings suggest important differences between the two CB1 receptor agonists in terms of their pharmacological effects.     

Time-course of the effects of chronic delta 9-tetrahydrocannabinol on behaviour, body temperature, brain amines and withdrawal-like behaviour in the rat

The effects of clomipramine HCl (15 mg kg-1 i.p.) on behaviour, body temperature and brain amines were investigated in rats that had been chronically treated twice daily with increasing doses of delta 9-tetrahydrocannabinol (delta 9-THC, 2-6 mg kg-1 i.v.). delta 9-THC produced a biphasic change in behaviour, stimulation followed by depression, and a pronounced hypothermia. Tolerance developed rapidly to these effects of delta 9-THC. Chronic treatment with delta 9-THC reduced the levels of homovanillic acid, 5-hydroxytryptamine and noradrenaline. The level of dopamine was not altered with chronic treatment and tolerance appeared to develop to the increased levels of 5-hydroxyindoleacetic acid induced by delta 9-THC. Injection of clomipramine, 12-14 h after 2, 5 or 10 days of delta 9-THC treatment induced characteristic changes in the rats behaviour which consisted of writhes, backward kicking, wet shakes, jumps ataxia and front paw and whole body tremor. The severity of the behavioural changes appeared to be dependent on the period of delta 9-THC administration and they were not accompanied by a change in body temperature or consistent changes in brain amines or metabolites. The results indicate that physical dependence on delta 9-THC may occur since clomipramine is able to precipitate changes in behaviour, indicative on an abstinence syndrome, in rats chronically treated with delta 9-THC. It is suggested that tryptaminergic mechanisms are altered during chronic delta 9-THC treatment and that clomipramine induces the behavioural changes by interacting with an altered tryptaminergic system.     

Effects of chronic administration of delta 9-tetrahydrocannabinol on the cardiovascular system, and pressor and behavioral responses to brain stimulation in freely moving rats

The effects of chronic administration of delta 9-THC on the cardiovascular system, and the pressor and behavioral responses to brain stimulation were investigated in freely moving rats with chronic electrode and arterial cannula implants. delta 9-THC at a dose of 6 mg/kg was injected intraperitoneally once a day for 10 days through an abdominal cannula. On the first day, delta 9-THC induced a significant decrease in heart rate and rise in blood pressure. The animals exhibited abnormal behavior such as catalepsy, walking backward and pivoting. On the 5th day, the bradycardia induced by delta 9-THC markedly decreased and on the 10th day tachycardia was observed. The pressor effect of delta 9-THC significantly increased on the 5th and 10th days. However, delta 9-THC-induced abnormal behavior was observed without any changes following chronic administration. delta 9-THC inhibited the pressor response and behavioral changes to electrical stimulation of the posterior hypothalamus and midbrain reticular formation. No tolerance developed to these depressive effects of delta 9-THC after chronic treatment. These data suggest that tolerance develops only to bradycardic effect of delta 9-THC and that the decrease in vagal activity may play some role in the development of tolerance.     

Ondansetron inhibits a behavioural consequence of withdrawing from drugs of abuse

The ability of the selective 5-HT3 receptor antagonist ondansetron to influence the behavioural consequences of withdrawal from chronic treatment with ethanol, nicotine or cocaine was investigated in the light/dark exploration test in the mouse and social interaction test in the rat. In both tests acute and chronic (7 days) treatments with ondansetron (0.01-1.0 microgram.kg-1 IP) disinhibited suppressed behaviour; withdrawal from chronic treatment (0.1 mg/kg IP b.i.d.) did not exacerbate the behavioural suppression. Chronic treatment for 14 days with ethanol (8% w/v in the drinking water), nicotine (0.1 mg/kg b.i.d.) or cocaine (1.0 mg/kg b.i.d.) released suppressed behaviour in the mouse and rat tests. Behavioural suppression was increased following withdrawal from ethanol, nicotine and cocaine. The administration of ondansetron (0.01 mg/kg IP b.i.d.) during the period of ethanol, nicotine and cocaine withdrawal prevented the exacerbation in suppressed behaviour. It is concluded that ondansetron potently reduces behavioural suppression during acute and chronic treatments in the rodent models, does not cause a rebound exacerbation of behavioural suppression following withdrawal, and is a highly effective inhibitor of the increased behavioural suppression following withdrawal from the drugs of abuse: ethanol, nicotine and cocaine.     

Cyamemazine decreases ethanol intake in rats and convulsions during ethanol withdrawal syndrome in mice

The effect of cyamemazine a dopamine D₂ receptor antagonist on voluntary ethanol consumption in rats and on ethanol withdrawal in mice was examined. Male Sprague-Dawley rats were tested in a free choice (water and 10% ethanol) experiment and consumed 5 g/kg ethanol daily. Rats were treated daily IP with cyamemazine ( 0.5, 1, or 2 mg/kg) or acamprosate (100 mg/kg) during 2 weeks. Both acamprosate and 1 mg/kg cyamemazine significantly decreased ethanol intake by 45% without affecting either fluid or food intake. The lowest dose of cyamemazine had no effect on alcohol intake but increased food intake. The highest dose had no effect on any variables. During the post-treatment period, only 1 mg/kg cyamemazine decreased both ethanol and fluid intakes. Mice were made dependent on alcohol using a chocolate fluid diet containing increasing concentrations of alcohol and withdrawn after 9 days. Mice were treated with cyamemazine (1 or 0.5 mg/kg, respectively) or with the same doses of lorazepam acutely on the day of withdrawal or chronically (during alcohol treatment). Both chronic and acute cyamemazine and lorazepam treatments decreased convulsions during ethanol withdrawal. Both acute treatments decreased locomotor activity in control and alcohol dependent mice. Chronic treatment had no effect on locomotor activity. We suggest that cyamemazine could reduce alcohol consumption by antagonizing the activation of the dopaminergic pathways during the induction of alcohol dependence. The action of cyamemazine on 5-HT₃ receptors could also explain its effect on alcohol convulsions during withdrawal convulsions. Received: 19 October 1997/Final version: 6 April 1998     

Dependence on and preference for morphine. (III) Improvement of spontaneous drug intake after combined treatment with morphine and cocaine]

One group of rats (n equals 6) was allowed free access to food combined with morphine and cocaine for 3 weeks, another group combined with either morphine or cocaine alone for 3 weeks. Intensity of decrease in body weight by withdrawal and ratios of spontaneous morphine and cocaine intake were compared, and the cross-spontaneous drug intake between morphine and cocaine using cocaine and morphine dependent rats was investigated, respectively. The results indicate that (a) decreased rate in body weight by withdrawal after 3 weeks administration with morphine-cocaine mixtures increased slightly, and spontaneous intake ratio for the higher drug-admixed food during administration period was also slightly increased as compared with a morphine added diet alone. (b) However, spontaneous intake ratio of both morphine [morphine (1 mg/g of food) vs. a normal diet (N.D.)] and cocaine [cocaine (2 mg/g of food) vs. N.D] increased 30 and 50 approximately 60% respectively, and these changes were maintained for about two months. (c) Spontaneous cocaine intake ratio after 3 weeks administration of morphine was almost the same level as that in cocaine dependent rats and decreased dependently when the administration period was extended. Spontaneous morphine intake ratio after 3 weeks administration of cocaine was 20% lower in total daily intake ratio as compared to morphine dependent rats, but spontaneous morphine intake ratio as compared to morphine dependent rats was gradually increased as in morphine dependent rats. (d) Furthermore, morphine-quinine combined treatment and cocaine or codeine treatment had no effect on spontaneous intake of quinine. These data suggest that combinations of morphine and cocaine have promoting properties of morphine and cocaine intake, respectively. Cross-spontaneous drug intake between morphine and cocaine was successful only in cocaine dependent rats using this method.     

Food,water and ethanol consumption by rats under a fixed-interval schedule of food presentation

Rats could lever press 24 hours a day for 97 mg food pellets under a fixed-interval (FI) 90 second schedule. During the first 4 days, an ethanol solution was the only available fluid, after which both water and ethanol solutions were available. At ethanol concentrations (w/v) of 5%, 7.5% and 10%, total caloric intake and total fluid intake remained constant, while ethanol consumption was inversely proportional to the concentration of the solution. When the FI 90 s schedule was changed to FI 45 s, or to FI 180 s, there were only small changes in total caloric intake, total fluid intake and in percentages of total fluid consumptipn and total caloric intake as ethanol. The data suggest that the intake of ethanol under this fixed-interval schedule depends more on the ethanol concentration than on the calories obtained from ethanol drinking.     

Schedule-induced oral self-administration of cocaine and ethanol solutions: lack of effect of chronic desipramine

Groups of rats drinking either solutions of cocaine HCl (0.16 mg/ml), ethanol (2.5% v/v), or water, drank excessive, equivalent volumes in daily, 3-h sessions of food-pellet delivery under a fixed-time 1-min (FT 1-min) schedule. During single-session exposures to pellet-delivery schedules using longer inter-pellet values (FT 3- or 5-min probe sessions), the cocaine and ethanol groups, but not the water group, drank greater ml/pellet amounts, confirming previous research. Inasmuch as enhanced ml/pellet intake during the greater FT probes correlated with the abuse potential of the drinking solution in previous research, the effect of chronic desipramine HCl (2 mg/kg, i.p. daily) on this enhanced intake response was determined. For all groups, chronic desipramine treatment (2 mg/kg was judged to be the maximum dose free of non-specific, suppressive effects) affected neither FT 1-min schedule-induced polydipsia nor did it affect the enhanced ingestional response to the greater FT probes for the cocaine and ethanol groups. Chronic administration of desipramine may have therapeutic efficacy in treating cocaine abuse only in subjects attempting to refrain from cocaine who are aided in their passage through a withdrawal phase by desipramine.     

Delta9-THC induced hyperphagia and tolerance assessment: interactions between the CB1 receptor agonist delta9-THC and the CB1 receptor antagonist SR-141716 (rimonabant) in rats

This study examined effects of the CB1 receptor antagonist/inverse agonist SR-141716 and the CB1 receptor agonist delta9-tetrahydrocannabinol (delta9-THC) on feeding behavior in male Sprague-Dawley rats. Rats were housed individually with free access to regular pelletized laboratory chow [after a 2 weeks handling phase, animals had access to regular chow for 21 h (Study 1) or 22 h (Study 2); high-fat powder food for 3 h in Study 1 and 2 h in Study 2, respectively], and free access to water. Animals were maintained on a reversed 12-h light/dark cycle (dark beginning at noon). Rats were habituated to this type of feeding and light/dark schedule for 3 weeks until a stable baseline for food intake was achieved. In Study 1, animals were examined after administration of delta9-THC alone (dose range 0.1-1.8 mg/kg), SR-141716 alone (dose range 0.03-0.3 mg/kg), and the two drugs combined; injections were given i.p. at the beginning of the second hour after presenting the high-fat diet and drugs were given twice weekly. There was a dose-related increase in high-fat diet intake, peaking at 0.56-1 mg/kg delta9-THC. SR-141716 alone suppressed the high-fat diet intake below control levels. A combination of 0.3 mg/kg SR-141716 and 0.56 mg/kg delta9-THC counteracted the effects on consumption of either drug alone. In Study 2, experimental rats were treated initially with 0.56 mg/kg delta9-THC for six consecutive days; controls received vehicle. Attenuation of the hyperphagia (high-fat diet) was evident after the second injection. Increasing doses of delta9-THC (1 and 1.8 mg/kg, for two and three consecutive days, respectively) did not reinstate the initial hyperphagia. In conclusion, low-to-moderate doses of delta9-THC produced hyperphagia (to a high-fat food source), which was antagonized by SR-141716. SR-141716 singly suppressed intake of the high-fat diet. Delta9-THC-induced hyperphagia dissipated rapidly upon chronic treatment; however, it is unclear whether this reflects pharmacological tolerance or the emergence of a conditioned taste aversion in Study 2.     

Anxiogenic effects of acute and chronic cocaine administration: neurochemical and behavioral studies.

The effects of cocaine on defensive withdrawal behavior in rats and elevated plus-maze behavior in mice were investigated. Cocaine (20 mg/kg IP) injected daily for 7 or 14 days induced defensive withdrawal; that is, the latency to emerge from a small chamber in an open field and the mean time in the chamber were both significantly increased. Acute cocaine administration also induced defensive withdrawal, and this effect was prevented by prior treatment with chlordiazepoxide (5 mg/kg IP). Both acute and chronic cocaine treatments significantly increased plasma concentrations of corticosterone and reduced the ratios of 3,4-dihydroxyphenylacetic acid to dopamine and 5-hydroxyindoleacetic acid to serotonin in several brain regions. Further evidence for an acute anxiogenic effect of cocaine was obtained from mice studied in the elevated plus-maze. Acute cocaine administration decreased both the number of entries into and the time spent in the open arms of the maze. These results taken together strongly support an anxiogenic action of acute and chronic cocaine administration.     

Voluntary alcohol and cocaine consumption in "low" and "high" stress plasma catecholamine responding rats

Alcohol (ethanol) and cocaine preference in a free-choice, two-bottle situation was measured in two groups of male and female "low" and "high" plasma catecholamine stress responding rats. Alcohol intake of a 5% solution (percent or mg/kg) showed markedly different but individually consistent intake among animals. "High" plasma catecholamine stress responders consumed more ethanol than did "low" responders. A similar finding was made when animals consumed a 10% solution; fluid intake fell but total ethanol intake remained the same. "High" responders drank more than did "low" responders. After a period of 4 weeks of water only, animals were reexposed to 5% ethanol and a significant positive correlation was seen in the drinking habits of the animals. Afterwards, exposure to a 0.02% cocaine solution resulted in cocaine intake which varied among animals, but was consistent for an individual rat and did not correlate with alcohol consumption. In general, ethanol and cocaine consumption correlated positively with the plasma catecholamine stress response. No significant differences in drinking habits were observed between the sexes. Thus, alcohol preference is a relatively stable characteristic of an animal, is higher in "high" as compared to "low" plasma catecholamine stress responders and does not correlate with voluntary cocaine consumption.     

Ethanol-reinforced behavior of rats with concurrent access to food and water

Dippers filled with water or an ethanol solution were presented to male Wistar rats contingent on lever-pressing under a concurrent fixed-ratio 1 (water) fixed-ratio 1 (ethanol) schedule. During Phase I, when maintenance feedings were given during instead of following the daily 3-h sessions, the feedings increased drinking of both 8% (w/v) ethanol and water, with 8% ethanol being consumed in greater volumes than water. In Phase II, a 28-day transitional period from the food-deprived to the food-satiated state, continuous access to food during 3-h sessions moderately decreased 8% ethanol intake, and increased water intake and total liquid intake (water plus 8% ethanol). In Phase III, concurrent water and ethanol intake of food-satiated rats was compared over two identical series of ethanol concentrations (8, 11.3, 16, 22.6, 32, and 8% retest). Food was freely available in both the operant conditioning chambers and home cages. The number of dipper presentations of ethanol exceeded presentations of water for each rat at each concentration studied. Presentations of water were low in number and did not vary with the ethanol concentration. As the ethanol concentration was increased, the number of ethanol presentations decreased, while the quantity consumed (mg/100 g body weight/h) generally increased.     

Estradiol protects against alteration of protein kinase C(epsilon) in a binge model of ethanol dependence and withdrawal

This study tested the hypothesis that a binge type of ethanol intake and ethanol withdrawal disturbs protein kinase C (PKC) homeostasis in a manner protected by 17beta-estradiol. Ovariectomized rats implanted with 17beta-estradiol or oil pellets received ethanol (7.5% weight/volume, 7 days) or control solution by a gavage method. The cerebelli were collected during ethanol exposure or ethanol withdrawal to assess the activity, protein levels, and cellular distribution of PKC(epsilon) and total PKC, using an ATP phosphorylation and immunoblot assays. While both ethanol exposure and ethanol withdrawal increased membrane protein levels and membrane translocation, only ethanol withdrawal enhanced activity of PKC(epsilon). Ethanol withdrawal not ethanol exposure increased the three parameters of total PKC. 17beta-Estradiol treatment prevented these changes in PKC profiles. These data suggest that an excessive episodic intake of ethanol followed by ethanol withdrawal disturbs PKC homeostasis and cellular distribution of PKC, in particular PKC(epsilon), in a manner that is protected by estrogen. PKC(epsilon) appears more vulnerable during ethanol withdrawal than during ethanol exposure.     

Neuropeptide Y administration into the third ventricle does not increase sucrose or ethanol self-administration but does affect the cortical EEG and increases food intake

RATIONALE: Several studies have provided indirect evidence that neuropeptide Y (NPY) may play a role in the regulation of ethanol consumption. However, the direct effects of central NPY administration on ethanol drinking are unclear. OBJECTIVE: This study examined the effects of NPY on ethanol, sucrose, and food consumption as well as its concomitant effects on the cortical EEG. METHODS: Wistar rats were implanted with cortical recording electrodes and a cannula in the third ventricle after using a sucrose substitution procedure to establish ethanol self-administration. NPY (0-15 microg/3.0 microl) was infused into the third ventricle prior to drinking sessions, when 10% ethanol (10E), 2% sucrose (2S), 0.5% sucrose (0.5S), or food were available. Behavior and cortical EEG were monitored during the sessions. RESULTS: NPY had no effect on the intake of 10E, 2S, or 0.5S, but NPY (15 microg/3.0 microl) significantly increased food intake. Under baseline drinking conditions, EEG power in the 6-8 Hz range was significantly greater when 2S was consumed compared to 10E. NPY decreased power in the 8-16 Hz range, decreased peak frequency in the 6-8 Hz range, and increased peak frequency in the 32-50 Hz range when 10E or 2S was available. CONCLUSIONS: These data suggest that NPY administration into the third ventricle preferentially regulates feeding compared to ethanol or sucrose drinking. In addition, since NPY significantly altered the cortical EEG in the absence of effects on ethanol and sucrose consumption, these data may indicate that NPY's cortical EEG effects are more related to its sedative or anxiolytic properties, rather than any effect on consumption.     

Effects of the administration of coca alkaloids on the primary immune responses of mice: interaction with delta 9-tetrahydrocannabinol and ethanol

The effects of cocaine, its metabolites, and other alkaloids from Erythroxylon coca on the primary immune responses of ICR mice to sheep red blood cells (sRBC) and dinitrofluorobenzene (DNFB) were studied. The Jerne hemolytic plaque assay (PFC) was used to evaluate the humoral immune response to sheep red blood cells, and the delayed type hypersensitivity (DTH) response to DNFB was used to study cellular immune responsiveness. Drugs were given in single daily po doses for 5 consecutive days beginning on the day of immunization or 3 days prior to and on Days 3 and 4 after immunization. Inhibition of both PFC and DTH responses occurred at doses of 15 to 60 mg/kg of cocaine and was greatest when fed during immunization. Five other alkaloids also suppressed the PFC and/or DTH response. Cocaine was more suppressive than the six other alkaloids tested. Ethanol (5 g/kg) did not suppress the DTH response and only marginally suppressed the PFC response. delta 9-THC inhibited the PFC response at doses of 10 mg/kg and marginally suppressed the DTH response at doses of 30 mg/kg, but not at other doses ranging from 10 to 90 mg/kg. Coadministration of 5 g/kg ethanol and 15 mg/kg cocaine resulted in 50% antagonism of effects of cocaine on the PFC response and complete antagonism of the suppression of the DTH response, but only if these substances were given during the period of immunization. Like ethanol, delta 9-THC also abolished the inhibitory effects of cocaine on the PFC and DTH response but only if coadministered during the period of immunization. Coadministration of ethanol and delta 9-THC resulted in synergistic inhibition of both DTH and PFC responses.     

A concurrently available nondrug reinforcer prevents the acquisition or decreases the maintenance of cocaine-reinforced behavior

Lever-Pressing responses of 55 rats were reinforced with IV-delivered cocaine (0.2 mg/kg) or saline under conditions of continuous access for 15 24-h sessions. The rats also responded on tongue-operated drinking devices for deliveries of a 3% (w/v) glucose +0.125% (w/v) sacharin (G+S) solution or water. The effects of removing these substances on behavior maintained by G+S, water, cocaine, or saline were compared in 11 groups. Terminating cocaine access produced a decrease in G+S drinking and an increase in food and water intake. In contrast, a group of rats that did not initially self-administer G+S showed increases in G+S drinking when cocaine was removed, and G+S-maintained responding persisted when cocaine was reinstated. Substitution of water for G+S produced a nearly two-fold increase in cocaine-reinforced behavior but no change in IV-delivered saline self-administration in a control group. A group that did not initially self-administer cocaine increased its infusion rate to over 400 infusions per day as soon as G+S was replaced with water. The effect of presenting cocaine to a group that responded for G+S alone was to decrease G+S intake, but there was only a a transient decrease in water intake in the control group. Likewise, presentation of G+S to a group of rats self-administering cocaine resulted in a decrease in infusions, but saline infusions did not change in a control group. Generally, there was an increase in food and water intake during cocaine removal, but food and water intake did not vary systematically with the removal or presentation of G+S. The results suggest that behavior reinforced by IV-delivered cocaine can be substantially altered by the discontinuation or presentation of G+S, an orally self-administered nondrug reinforcer.     

Effects of acute delta 9-THC administration on EEG and EEG power spectra in the rat

This study was designed to determine the acute effects of delta 9-THC on the cortical EEG with the spectral analysis technique. Adult female Sprague-Dawley rats were implanted with chronic cortical and temporalis muscle electrodes. Intraperitoneally administered delta 9-THC (5 and 10 mg/kg) produced a reduction in peak-to-peak voltage of the desynchronized cortical EEG during wakefulness. Associated spectral power was reduced to about 50% of control during the first hour after injection of delta 9-THC and gradually returned toward the control value over an 8-hr period. Occurrences of delta 9-THC-induced high-voltage EEG bursts, overriding the reduced EEG tracing, were associated with an EEG spectral peak at 6 Hz. The first few slow-wave sleep (SWS) episodes appearing after delta 9-THC administration were associated with more slow-frequency waveforms and more slow-frequency spectral power than with control slow-wave sleep episodes. During control rapid eye movement (REM) sleep episodes, an EEG theta wave pattern, with an associated spectral peak at about 8 Hz, was characteristic. Conversely, the first few REM sleep episodes emerging after delta 9-THC administration contained overriding high-voltage bursts, the related power spectra of which had two peaks at about 7 and 11 Hz.     

Control of alcohol addiction by SKV therapy--its action on water, food intake, brain function and cell membrane composition

Alcohol being easily permeable through cell membrane causes toxic damage to many tissues. Rats drinking aqueous ethanol (25% v/v) for 120 days and 240 days showed an initial rise in body weight. The reduced rate in weight gain in chronic alcoholism is associated with a fall in food intake. Ethanol ingesting animals showed slow response to stimuli and increase in blood ethanol and serum GGTP levels. Liver plasma membrane, kidney brush-border membrane and pancreatic plasma membrane from alcoholic rats showed significant alterations in cholesterol/phospholipid molar ratio and membrane ATPases. Water retention with the enlargement of liver and kidney associated with increased fluid consumption are also seen during alcoholism. SKV by breaking alcohol dependence reduces drinking, lowers blood ethanol level and fluid intake without developing withdrawal symptoms. Restriction of ethanol intake by SKV therapy resulted in the reversal of organ enlargement and membrane composition in alcoholics.