Errol Yudko

Defense system psychopharmacology: an ethological approach to the pharmacology of fear and anxiety.

Defensive behaviors comprise a set of flexible and adaptive responses to threatening situations and stimuli. In semi-natural situations affording a wide variety of responses, defensive behaviors change over time in response to information about the presence of danger, acquired through risk assessment activities. Two test batteries, a Fear/Defense Test Battery (F/DTB) measuring defensive behaviors to present, approaching predators, and an Anxiety/Defense Test Battery (A/DTB) measuring reactions to potential threat, have been used in conjunction with administration of potentially anxiolytic drugs. Results suggest that the F/DTB behaviors are not systematically responsive to anxiolytics. However, on the A/DTB, anxiolytic benzodiazepines produce a profile of effects primarily involving risk assessment activities. Very similar profiles of effect are seen also with some 5-HT1A compounds, alcohol, imipramine and MK-801, but not for a variety of additional compounds. A consistent pattern of gender differences are obtained with the A/DTB, with females more defensive than males. These results indicate that particular patterns of defensive behaviors may provide a very appropriate animal model for the analysis of pharmacological effects on anxiety.

Hits (not Discussion Posts) predict student success in online courses: A double cross-validation study

The efficacy of individual components of an online course on positive course outcome was examined via stepwise multiple regression analysis. Outcome was measured as the students total score on all exams given during the course. The predictors were page hits, discussion posts, and discussion reads. The vast majority of the variance of outcome was accounted for by total page hits. Participation in discussion had little to no effect on performance as measured by outcome on exams. The results were double cross-validated with a sample chosen from another class. There was no shrinkage, indicating that the equations derived from the two samples were very reliable.

Chronic social stress: Changes in behavioral and physiological indices of emotion

Subordination constitutes a natural and often chronic stress condition for males of virtually all species of social mammals. Subordinate male rats of mixed-sex groups maintained in visible burrow systems show high-magnitude changes in adrenal and gonadal steroid hormones and, in a subpopulation, disruptions in hypothalamic pituitary adrenal axis function. Changes in brain serotonin systems have been extensively documented in both colony subordinates and colony dominants, with other regional neurotransmitter system changes also indicated. The group experience seems to change a variety of behaviors both inside the colony situation and in tests run outside the colonies and may disrupt the relationship found in controls between hypothalamic pituitary adrenal response to an acute stressor and defensive behavior. Comparisons of these patterns of stress response with those of other chronic stress models such as learned helplessness and chronic mild stress suggest that, in terms of adrenal and gonadal steroid hormone response, subordination constitutes a more severe stressor. Some involvement of the serotonin system has been demonstrated for both subordination and more traditional models, and other systems may prove to be involved in both. However, a central feature of both learned helplessness and chronic mild stress paradigms is a specific criterion behavior or behaviors, emphasized as models for particular psychopathologies. Thus, learned helplessness and chronic mild stress studies have tended to emphasize the effects of pharmacological agents on these models, whereas work with subordination has been focused on analysis of the biobehavioral stress process itself.

High-frequency (35-70 kHz) ultrasonic vocalizations in rats confronted with anesthetized conspecifics: effects of gepirone, ethanol, and diazepam.

The effects of three anxiolytics--gepirone, diazepam, and ethanol--on high-frequency ultrasonic vocalizations elicited from rats via a new method are described. Subjects confronted with an anesthetized, same-sex conspecific in a neutral test cage emitted ultrasonic vocalizations in the 35- to 70-kHz range. The great majority of these were calls with frequencies higher than 40 kHz; of these, short calls (< 50 ms) occurred significantly more frequently than long calls (> 50 ms). Female subjects emitted far more of these high-short and high-long vocalizations than males did. In females, but not males, these calls were reduced in number by gepirone, 5-hydroxytryptamine1A (5-HT1A) agonist, at both 1.0- and 10.0-mg/kg doses and by diazepam, a benzodiazepine, at 3.0 but not 1.0 mg/kg. Ethanol (0.6 and 1.2 g/kg) had no detectable effect. The utility of this method, both for the study of ultrasounds and assessment of serotonergic anxiolytics, is discussed.

Emerging themes in preclinical research on alcohol and aggression

Animal research into the alcohol-aggression relationship is based on a need to understand this relationship in people, and its success depends on the degree to which animal models can provide appropriate parallels to relevant human phenomena. Comparisons of human and animal literature suggest that parallels may be found for the following: alcohol enhances aggression in some, but not all individuals; consumption increases the probability of victimization (being attacked by a conspecific); alcohol reduces anxiety, and socially stressed individuals show increased voluntary consumption; alcohol reduces avoidance of threatening situations or stimuli and may place individuals at greater risk of being attacked; both anxiety reduction and decreased avoidance of threat may increase the probability of involvement in violent situations. These findings suggest that a variety of mechanisms may be involved in alcohol enhancement of aggression. Differences in effects of alcohol on human, as opposed to animal, aggression may reflect specific human capabilities. Although high doses of alcohol consistently reduce aggression in laboratory animals, this may reflect motoric and sedative effects that are not relevant for human behavior, in which verbal aggression and aggression involving the use of weapons make motor capability less important. Human voluntary alcohol consumption may also reflect response to stressors that also simultaneously promote aggression, a situation not paralleled by animal studies in which the drug is administered rather than voluntarily consumed. Nonetheless, obtained parallels suggest that animal experimentation using ecologically relevant situations can provide highly generalizable analyses of the alcohol-aggression relationship.

Reaction Times to Words vs Symbols for Both Hands

Reaction times were used to infer an interaction between different stimuli (verbal and symbolic) and the hand used to respond to such stimuli for 26 college students. Significant differences in reaction times were found dependent upon whether the stimulus was a word or a symbol and which hand was used in response to the different stimuli. There was more rapid mediation with significantly shorter latency for symbolic stimuli than for verbal stimuli for both the right and left hands. Also, latency was shorter for symbolic stimuli using the right hand than for verbal stimuli using the left hand. It may be concluded from this that efficacy of symbolic stimuli is primary in conveyance of denotative meaning. The primacy of symbolic stimuli for denoting meaning might be traced to evolutionary sources.

Effects of Methamphetamine Use

The cerebral damage caused by methamphetamine intoxication can be formidable. Prolonged use is associated with injury to the dopamine system. Essentially, continued methamphetamine use likely leads to axonic degeneration of the dopamine axon terminals in the striatum, frontal cortex, nucleus accumbens, and amygdala. Hypersensitization of neurons occurs, for example, in increasing sensitivity of D-1 receptors. It is important to note that changes in catecholamines alone cannot explain behavior in humans when they are methamphetamine intoxicated. Animal studies across several species demonstrate that high dosages of methamphetamine damage nerve cells (Swan, 1997). In rats, one high dose is enough to cause damage to neurons; prolonged administration increases the number of neurons that are killed off (Swan, 1997). In squirrels, a single dose of MDMA (which is structurally similar to methamphetamine and mescaline) in only slight doses significantly damages brain neurons that produce serotonin. Twelve to 18 months after exposure, serotonin-producing nerves grow abnormally or not at all. MDMA selectively damages serotonin neurons in virtually all species (Fischer et al., 1995). Buffenstein et al. (1997) showed through SPECT scanning of methamphetamine abusers in Hawaii that brain deterioration continues for months after abstinence, a finding that, if consistently cross-validated, suggests another unique and pathological feature of methamphetamine. Not surprisingly, high doses of methamphetamine can cause death. A male under arrest died with a blood content greater than 60 mg per liter after swallowing a “baggie” of methamphetamine (Logan et al., 1996). A toxic reaction in humans can occur at levels as low as 50 mg of pure methamphetamine 6