Memory formation: evidence for a specific neurochemical system in the amygdala.

beta-Adrenergic antagonists injected into the amygdala complex of rats trained in a passive avoidance task produced time-dependent and dose-dependent decreases in retention of the task. In addition, the effects observed with beta-adrenergic antagonists were both stereospecific and reversed by norepinephrine. The results support a role for an amygdala beta-adrenergic system in memory processes.

Associative control of tolerance to the sedative effects of a short-acting benzodiazepine.

The role of Pavlovian conditioning in tolerance to the depressant effect of a benzodiazepine (midazolam) on the ambulatory activity of rats was examined. The depression of activity by low doses (1.0 and 4.0 mg/kg, ip) of midazolam diminished quickly over repeated doses given at 48-hr intervals (Experiment 1). Equivalent tolerance was observed in groups measured at 2 min and 30 min after drug injection. When challenged with saline, however, drug-tolerant animals tested immediately after injection were hyperactive in comparison with nontolerant controls, whereas equivalent groups tested 30 min after injection were not. A second context was designed, and its discriminability from the original was established by assessing context-specific suppression of activity following exposure to mild electric shock (Experiment 2). In Experiment 3A, although tolerant animals tested in the drug-associated context remained fully tolerant, a second group demonstrated a complete loss of tolerance when given the drug in a saline-associated context. Both groups were fully tolerant when tested again in the drug-associated context after 14 drug-free days. In Experiment 3B, tolerance was significantly reduced by 14 extinction exposures to the drug-associated environment without the drug. These results are uniquely predicted by associative models of drug tolerance and may have implications for the clinical use of this class of drugs.

6-Hydroxydopamine and the aggressive behavior induced by marihuana in REM sleep-deprived rats.

6-Hydroxydopamine (6OH-DA) pretreatment increased the aggressive behavior induced by marihuana in REM sleep-deprived rats. Brain catecholamine assays revealed that 6OH-DA depleted popamine (DA) and norepinephrine (NE) to a different extent, increasing the DA/NE ratio. Intraventricular injection of NE significantly decreased the aggressive behavior of these animals, whereas control solution or DA injections had no effect. The possible role played by DA and NE in the aggressive behavior induced by marihuana in REM sleep-deprived rats is discussed.

Phencyclidine produces aggressive behavior in rapid eye movement sleep-deprived rats.

This study examined effects of acute doses of phencyclidine (PCP; 0.025, 0.05, 0.10, and 0.20 mg/kg intraperitoneally) on intra-specific aggressive behavior and muricide in normal rats and rats deprived of rapid eye movement (REM) sleep. Dose-related changes in intra-specific aggression and muricide occurred in REM sleep-deprived rats only. Dose-response curves are inverted-U shaped with the .05 mg/kg dose producing increases in aggression. Intra-specific aggression and muricide may serve as models of PCP-induced aggression in humans.

Relationships between motivation and depression in chronic marijuana users.

The "amotivational syndrome" which has been associated with marijuana use has not been examined systematically in relation to marijuana use and mental health. Light and heavy users were solicited by personal contact. They were asked to complete anonymous questionnaires which measured marijuana, alcohol and cocaine use, perceived states during marijuana intoxication, depressive symptoms in the last year, the Orientation to Life Scale and a modified form of the Thematic Apperception Test, from which Need for Achievement, Affiliation and Power were assessed. Several group comparisons were made: Chronic heavy-users (medians: daily use for 6 years) with and without significant symptoms of depression within the last year were compared with Light users (medians: several times per month for 4.5 years) with and without significant symptoms of depression within the last year. Subjects in all groups reported similar ratings of intoxication (being stoned) during marijuana use. No differences were found in alcohol or cocaine use among the comparison groups. Scores on Need for Achievement were significantly lower in heavy users with depressive symptoms when compared with all other groups. No effects were found among groups in measures of the Need for Affiliation and the Need for Power. Both light and heavy users with symptoms of depression had significantly lower scores than those without depressive symptoms, on the overall Orientation to Life questionnaire and on each subscale measuring Meaningfulness, Manageability and Comprehensibility. These data suggest that amotivational symptoms observed in heavy marijuana users in treatment are due to depression.

Interstrain aggression in hypertensive and/or hyperactive rats: SHR, WKY, WKHA, WKHT.

Four inbred rat strains, all derived from Wistar-Kyoto (WKY) rats, express hypertension and hyperactivity in all combinations: SHRs have both traits, WKYs have neither, WKHAs are hyperactive/normotensive, and WKHTs are hypertensive/normoactive. Rats of the four strains were tested for aggression, at one time only, by pairing subjects of same sex, same age, but different strain, in a novel arena, i.e., on neutral ground, for three consecutive, 5-min observation periods. Total aggression scores were highest in females, highest in the first 5-min period, and lower at 7-9 months than at younger ages. Allogrooming was more frequently observed than other types of aggression, such as attacks, mounts, aggressive postures, and blocks. Allogrooming scores were significantly elevated in the hypertensive strains, especially WKHT, and very low in the hyperactive strains, especially WKHA. The other forms of aggression were significantly higher in females with hyperactivity. It was concluded that interstrain aggression, as seen in SHRs and WKYs, is differentially expressed by two new strains genetically derived from them. Furthermore, no one strain among these four expresses all components of the behavioral responses seen in this form of aggression.

Criterion for learned helplessness in the rat: a redefinition.

Numerous investigators have reported difficulty obtaining reliable learned helplessness. Various laboratories have used differing test environments and criteria, making comparisons among experiments difficult. Some use an escape deficit criterion, in which escape is slowed down in a shuttle box, while others have used an escape failure criterion, in which rats do not escape at all on most test trials. Little work has been done to test the validity of LH, i.e., the prediction of persistence of escape failure after exposure to uncontrollable shock. The present studies demonstrate that the reliability and validity of learned helplessness can be improved by 1) modifying the shuttle box to increase task difficulty and decrease random escape behavior and 2) adopting a new escape failure criterion for helpless behavior which is based on statistical prediction of the persistence of escape deficits.

Effects of marijuana extract distillate and cannabidiol on variable interval performance as a function of food deprivation.

Lever-pressing rates plotted as a function of number of hours of food deprivation produces an inverted U curve, the activation performance curve. Since delta 9-tetrahydrocannabinol depresses the response rate on variable interval (VI) performance, it may be that the response depression reflects changes in this curve. Rats were tested VI performance at five levels of food deprivation and were treated with a vehicle control, marijuana extract distillate (MED) at 7.5 and 11.25 mg/kg, cannabidiol (CBD), at 15 mg/kg or combinations: 7.5 mg/kg MED + 15 mg/kg CBD and 11.25 mg/kg MED + 15 mg/kg CBD. MED produced a depression of VI performance which was greatest at low levels of deprivation. CBD did not depress performance. When CBD was conbined with MED, potentiation of depression occurred. The potentiation depression was not additive, but occurred at high levels of deprivation. It appears that MED depresses performance most at low levels of deprivation and that CBD potentiates the depression produced by MED at high levels of deprivation.

Effects of delta9-tetrahydrocannabinol on active avoidance acquisition and passive avoidance retention in rats with amygdaloid lesions.

Delta9-Tetrahydrocannabinol was administered to rats with basolateral amygdaloid lesions, control rats, and normal rats in doses of 0.75, 1.5, and 3.0 mg/kg i.v. They were trained in a one-session two-way active avoidance task. Delta9-Tetrahydrocannabinol increased the percentage of avoidance and the intertrial crossing rates in all groups, regardless of lesion treatment. Rats with basolateral amygdaloid lesions were not different from controls on any measure. In a second experiment, delta9-tetrahydrocannabinol was administered to rats with basolateral amygdaloid lesions and control rats in doses of 0.75 and 3.0 mg/kg 24 h after learning of a one-trial passive avoidance task, and retention was measured. No differences were found as a function of drug treatment or lesion condition. It was concluded that the basolateral amygdala is not a necessary condition for the action of delta9-tetrahydrocannabinol on active avoidance acquisition, that the drug has no effect on passive avoidance retention, and the basolateral amygdala is not necessary for two-way active avoidance acquisition or passive avoidance retention. Active avoidance results are discussed in terms of a possible relationship between delta9-tetrahydrocannabinol, ACTH, and avoidance learning.

Characteristics of the stimulus produced by the mixture of cannabidiol with delta 9-tetrahydrocannabinol.

Rats, trained to discriminate between delta 9-THC (5 mg/kg) and a control solution, using a T-maze, were submitted to generalization tests wih delta 9-THC (2.5 and 1.25 mg/kg), CBD (40 mg/kg) and the mixtures of delta 9-THC (5 and 1.25 mg/kg) with CBD (40 mg/kg). Doses of delta 9-THC smaller than the training dose, produced a progressive reduction in the number of correct responses together with a decrease in the running time. The choice made by the animals under the effect of CBD (40 mg/kg) did not differ from that of the animals given the control solution but their running time was significantly longer. The mixtures of CBD (40 mg/kg) with delta 9-THC (5 and 1.25 mg/kg) produced approximately 50% response to both sides of the maze, and with run times greater than those observed with delta 9-THC (5 mg/kg). The results suggest that the simultaneous administration of the two cannabinoids might produce a qualitative stimulus different from that produced by delta 9-THC alone.

Effects of delta9-tetrahydrocannabinol and cannabinol in man.

The interaction of delta9-tetrahydrocannabinol (delta9-THC) and cannabinol (CBN) was studied in man. Five male volunteers were given placebo, 50 mg CBN, 25 mg delta9-THC, 12.5 mg delta9-THC + 25 mg CBN, and 25 mg delta9-THC + 50 mg CBN (orally). Administrations were spaced 1 week apart. With physiological measures, delta9-THC produced an increase in heart rate while CBN did not. When combined, no change of the delta9-THC effect occurred. No changes occurred on the electrocardiogram, blood pressure, or body temperature. With psychophysical measures no changes occurred in pain thresholds or skin sensitivity as a function of drug treatment. In time estimates of the passage of 1 minute, delta9-THC alone produced underestimates of the passage of 1 minute and CBN alone had no effect. In combination the two drugs had a tendency to produce significant overestimates and underestimates of the passage of 1 minute. On a 66-item adjective-pair drug reaction scale, the volunteers reported feeling drugged, drunk, dizzy, and drowsy under the delta9-THC condition, but not under the CBN condition. With combined drug treatment, volunteers reported feeling more drugged, drunk, dizzy, and drowsy than under the delta9-THC condition alone. None of the drug treatments produced significant changes on other items which included items on perception, emotion, cognition and sociability. It appears that CBN increases the effect of delta9-THC on some aspects of physiological and psychological processes, but that these effects are small and cannot account for the greater potency which has been reported when plant material is used.

Development and validation of the Biphasic Alcohol Effects Scale.

Alcohol produces stimulant and sedative effects, and both types of effect are thought to influence drinking practices. This article describes the development and preliminary validation of the Biphasic Alcohol Effects Scale (BAES), a self-report, unipolar adjective rating scale designed to measure both stimulant and sedative effects of alcohol. An initial pool of 12 stimulant and 12 sedative items was derived from previous alcohol effect measures, and from descriptors of intoxication generated by subjects during interviews conducted on both the ascending and descending limbs of the blood alcohol curve. This item pool was administered to a sample of sober college students twice, with a 2-week inter-test interval. Items that were difficult to comprehend, or that had high ratings or low test-retest reliability, were eliminated, resulting in a seven-item stimulant subscale and a seven-item sedative subscale. These subscales showed high internal consistency in a sober state, which was not improved by additional item deletion. The data from this study also provided a basis for revising the instructions for the BAES. The new 14-item instrument was then given to 30 male and 12 female nonalcoholics on the ascending and descending limbs of the blood alcohol curve, after the administration of either 0.75 ml/kg alcohol (males) or 0.65 ml/kg alcohol (females). Internal consistency was high for both BAES subscales on both limbs of the blood alcohol curve (Cronbach's alpha = 0.85 to 0.94), and was not improved by additional item deletion. Factor analyses conducted on both limbs of the blood alcohol curve supported the proposed factor structure of the BAES.(ABSTRACT TRUNCATED AT 250 WORDS)

Behavioral and metabolic effects of sucrose-supplemented feeding in hyperactive rats.

Two hyperactive rat strains [spontaneously hypertensive rats (SHR) and SHR-Wistar-Kyoto cross (WK-HA)] and their nonhyperactive genetic control strain (Wistar-Kyoto) were fed ad libitum sucrose-supplemented rat chow, or chow alone in controls, to determine the effects of dietary sugar on behavior. The diets were given either overnight (acute sugar) or for 14-18 days (chronic sugar), and testing was carried out on the morning after each of the dietary schedules. The metabolic studies revealed significant strain, sex, and age differences in appetite for sucrose, caloric intake, postprandial plasma levels of glucose and insulin, and weight gain after sucrose feeding. The findings indicate that sugar feeding led to increased plasma glucose and insulin levels; however, total caloric intake was decreased, and less weight gain was observed than in chow-fed controls, particularly among the hyperactive strains. In behavioral tests, sugar feeding did not alter spontaneous activity levels in any of the strains after either acute or chronic diets. There were also no significant effects of sucrose consumption on spatial learning and memory in a plus-shaped maze as determined by use of a shock-avoidance paradigm. The only significant behavioral effects of sucrose observed were an impairment in habituation and distractibility among the WK-HA females, the most hyperactive group among these strains.