Valeriana officinalis root extracts have potent anxiolytic effects in laboratory rats.

Valerian root (Valeriana officinalis) is a popular and widely available herbal supplement, primarily used to treat insomnia and anxiety. Until recently, its mechanism of action has remained unknown. Neurobiological research has begun to show that the herb, with its active valerenic acid, interacts with the GABA(A)-ergic system, a mechanism of action similar to the benzodiazepine drugs. This series of experiments sought to corroborate these findings with behavioral measures, compare them to the benzodiazepine diazepam, and to analyze the chemical composition of Valeriana officinalis. Rats were administered either ethanol (1 ml/kg), diazepam (1mg/kg), valerian root extract (3 ml/kg), valerenic acid (3mg/kg), or a solution of valerenic acid and exogenous GABA (75 microg/kg and 3.6 microg/kg, respectively) and assessed for the number of entries and time spent on the open arms of an elevated plus maze. Results showed that there was a significant reduction in anxious behavior when valerian extract or valerenic acid exposed subjects were compared to the ethanol control group. The evidence supports Valeriana officinalis as a potential alternative to the traditional anxiolytics as measured by the elevated plus maze.

Active cocaine immunization attenuates the discriminative properties of cocaine.

Anticocaine antibody, resulting from immunization with the cocaine-keyhole-limpet-hemocyanin (KLH) conjugate, weakened the ability of cocaine to act as a discriminative stimulus in rats. Subjects were given extensive training to discriminate 5.0 mg/kg of cocaine from saline prior to immunization. Several weeks following immunization with cocaine-KLH, subjects failed to reliably discriminate cocaine from saline. Nonimmunized control rats retained the ability to discriminate cocaine from saline throughout the experiment. These results further demonstrate that active immunization is effective in blunting cocaine effects. Immunized subjects were able to discriminate 20 mg/kg of cocaine, however, suggesting that anticocaine antibody may be overwhelmed by large cocaine doses.

Active immunization with cocaine-protein conjugate attenuates cocaine effects.

Immunization with cocaine-keyhole limpet hemocyanin (KLH) conjugate elicited the formation of anti-cocaine antibody sufficient to blunt the effects of cocaine in rats. Cocaine was bound to KLH for immunization with the photoactivatable crosslinker N-hydroxysuccinimide-4-azidobezoate (HSAB). Immunization with the cocaine-KLH-complete Freund's adjuvant complex was effective in attenuating the analgesic and reinforcing effects of cocaine in laboratory rats. Enzyme-linked dot blot assay revealed the presence of anti-cocaine antibody in serum. Competitive binding studies suggest that the antibody was specific to cocaine. Active immunization for cocaine may provide an alternative to drug treatment and may provide protection from addiction.

Focused US system for MR imaging-guided tumor ablation.

PURPOSE: To measure the performance characteristics of a focused ultrasound (US) system for magnetic resonance (MR) imaging-guided tumor ablation. MATERIALS AND METHODS: The authors constructed a focused US system for MR imaging-guided tumor ablation. The location of the heated region and thermal dose were monitored with temperature-sensitive MR images obtained in phantoms and rabbit skeletal muscle after application of each sonic pulse. RESULTS: The region heated by the focused ultrasound beam was within 1 mm of that observed on temperature-sensitive fast gradient-echo MR images of in vivo rabbit skeletal muscle. Analysis of heat flow and the rate of coagulation necrosis provided an estimate of the size of the ablated region that was in agreement with experimental findings. CONCLUSION: MR imaging provides target definition and control for thermal therapy in regions of variable perfusion or in tissues that are not well characterized.

Cholecystokinin, diet palatability, and feeding regulation in rats.

Rats ate less food than normal on cyclic-ratio schedules following cholecystokinin and lithium chloride injections. Nevertheless, they defended this lower eating rate in the same way as under control conditions. The pattern of effects produced by cholecystokinin and lithium chloride resembled those following diet adulteration with citric acid and sucrose octa acetate and differed from the effects produced by increases in body weight. Cholecystokinin and lithium chloride injections also produced similar changes in the free-feeding patterns of non-deprived rats: Both meal size and intermeal intervals decreased in manner similar to the effects of citric acid and sucrose octa acetate adulteration. Interpreted in terms of a static regulatory model, these results suggest that cholecystokinin and lithium chloride suppress feeding by degrading the palatability of food, not by promoting satiety, discomfort, or illness.

Operant regulation of feeding: a static analysis.

Cyclic-ratio schedules are a rapid method for studying the operant regulation of feeding rate. The cyclic method produces results comparable to traditional but time-consuming parametric methods. Performance on cyclic-ratio schedules is well described by a linear regulatory model that embodies three quantitative feedback assumptions: (a) that rate of feeding is regulated by the rate of operant behavior, (b) that taste factors have an additive effect on the rate of the operant response, and (c) that regulatory "gain" is inversely related to body weight. This model accurately describes poorer regulatory performance at high body weights and following amphetamine administration, and the effects of altered diet palatability on preferred feeding rates.

Decreased feeding associated with acute hypoxia in rats.

Rats obtained less food than normal on a cyclic-ratio schedule during brief, 1-hr exposure to either moderate hypobaric hypoxia (BP = 435 Torr, PO2 approximately equal to 91 Torr) or to hypoxic hypoxia (BP = 750 Torr, PO2, approximately equal to 90 Torr), but not during hypobaric exposure with 36.5% oxygen (BP = 435 Torr, PO2 approximately equal to 159 Torr). The depressed rate of feeding associated with hypoxia was nevertheless well regulated. Interpreted in terms of a regulatory model, these results suggest that hypoxia suppresses eating because it degrades the taste of food, not because it impairs feeding regulation or general activity.

Three versions of the additive theories of behavioral contrast.

The additive theories of behavioral contrast state that contrast will occur only when two types of responses interact during multiple schedules. Three more specific versions of the theories may be defined according to how they distinguish these two types of responses. A strong version physically distinguishes them. A second version distinguishes them according to the theoretical processes which control them. A weak version distinguishes them on the basis of the environmental relations which control them. Only the weak version of the theories is currently testable. The weak theory should be tested by establishing each of the two environmental relations independently and then combining them to assess their effect on behavior. Because this test is not usually performed, many of the results which have been taken to support or contradict the additive theories are actually ambiguous.

Contrast and undermatching as a function of reinforcer duration and quality during multiple schedules.

Eight pigeons pecked keys under multiple variable-interval two-minute variable-interval two-minute schedules. In Experiment 1, the reinforcers were 2, 4, or 8 seconds access to a food magazine. In Experiments 2 and 3, the reinforcers were grains that had been determined to be most-, moderately-, or non-preferred. Both positive and negative behavioral contrast occurred when the reinforcers in one component were held constant and the duration or type of reinforcer obtained in the other component varied. Undermatching occurred when the relative rate of responding during a component was plotted as a function of the relative duration of the reinforcers in that component.