Methylphenidate Attenuates Rats' Preference for a Novel Spatial Stimulus Introduced into a Familiar Enviroment: Assessment Using a Force Plate Actometer

Methylphenidate is a psychostimulant widely used in the treatment of attention deficit hyperactivity disorder (ADHD). Here we report a novel paradigm that affords inferences about habituation and attention to a novel stimulus in a familiar environment in a single test session without prior training of the animals. The paradigm was used to assess the effects of methylphenidate (2.5 and 5.0 mg/kg, sc) in young adult, male, Long-Evans rats. Methylphenidate increased locomotor activity during the initial exposure to the test apparatus in a non-dose-related manner. However, upon introduction of a novel spatial stimulus (an alcove) in the familiar environment, methylphenidate-treatment resulted in dose-related increases in distance traveled and inhibition of long dwell times in the alcove, the latter behavior being characteristic of vehicle-treated rats’ response to the alcove condition. These results demonstrate the utility of this paradigm in the elucidation of the behavioral effects of a drug commonly used in the treatment of ADHD. Findings also suggest that species-typical response preferences in rats (e.g., refuge-seeking) may emerge in experimental settings that add spatial novelty to otherwise featureless test enclosures commonly used to assess locomotor activity

Behavioral effects of chronic administration of psychoactive drugs to anxious patients

The effects of chronic administration of (a) 1600 mg. meprobamate, (b) five Tranquil tablets (the maximum recommended daily dose), and (c) placebos were examined, in a counterbalanced partially blinded design. Thirty-two subjects, including 23 anxious patients, employed as their own controls, were given behavioral tests, psychiatric interviews, and ratings at the end of each 21 day treatment period.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46328/1/213_2004_Article_BF00409114.pd

DEVELOPMENTAL EFFECTS OF DIETARY N-3 FATTY ACIDS ON ACTIVITY AND RESPONSE TO NOVELTY

Insufficient availability of n-3 polyunsaturated fatty acids (PUFA) during pre- and neonatal development decreases accretion of docosahexaenoic acid (DHA, 22:6n-3) in the developing brain. Low tissue levels of DHA are associated with neurodevelopmental disorders including attention deficit hyperactivity disorder (ADHD). In this study, 1st-and 2nd-litter male Long-Evans rats were raised from conception on a Control diet containing α-linolenic acid (4.20 g/kg diet), the dietarily essential fatty acid precursor of DHA, or a diet Deficient in α-linolenic acid (0.38 g/kg diet). The Deficient diet resulted in a decrease in brain phospholipid DHA of 48% in 1st-litter pups and 65% in 2nd-litter pups. Activity, habituation, and response to spatial change in a familiar environment were assessed in a single-session behavioral paradigm at postnatal days 28 and 70, inclusive. Activity and habituation varied by age with younger rats exhibiting higher activity, less habituation, and less stimulation of activity induced by spatial novelty. During the first and second exposures to the test chamber, 2nd-litter Deficient pups exhibited higher levels of activity than Control rats or 1st-litter Deficient pups and less habituation during the first exposure, but were not more active after introduction of a novel spatial stimulus. The higher level of activity in a familiar environment, but not after introduction of a novel stimulus is consistent with clinical observations in ADHD. The observation of this effect only in 2nd-litter rats fed the Deficient diet suggests that brain DHA content, rather than dietary n-3 PUFA content, likely underlies these effects

Time and dosage effects of meprobamate on visual detection

Sixteen male subjects, 21 years and older, were run in a doubleblind own-control design under three dosages of meprobamate (400, 800 and 1600 mg) and matching placebo, to determine response curves on a visual detection task over a four and one-half hour period, from 5:00 to 9:30 p.m. To control for possible daily cycle effects two additional runs under placebo and 1600 mg meprobamate were conducted from 8:00 a.m. to 12:30 p.m.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46406/1/213_2004_Article_BF00710913.pd

Prediction of Psilocybin Response in Healthy Volunteers

Responses to hallucinogenic drugs, such as psilocybin, are believed to be critically dependent on the user's personality, current mood state, drug pre-experiences, expectancies, and social and environmental variables. However, little is known about the order of importance of these variables and their effect sizes in comparison to drug dose. Hence, this study investigated the effects of 24 predictor variables, including age, sex, education, personality traits, drug pre-experience, mental state before drug intake, experimental setting, and drug dose on the acute response to psilocybin. The analysis was based on the pooled data of 23 controlled experimental studies involving 409 psilocybin administrations to 261 healthy volunteers. Multiple linear mixed effects models were fitted for each of 15 response variables. Although drug dose was clearly the most important predictor for all measured response variables, several non-pharmacological variables significantly contributed to the effects of psilocybin. Specifically, having a high score in the personality trait of Absorption, being in an emotionally excitable and active state immediately before drug intake, and having experienced few psychological problems in past weeks were most strongly associated with pleasant and mystical-type experiences, whereas high Emotional Excitability, low age, and an experimental setting involving positron emission tomography most strongly predicted unpleasant and/or anxious reactions to psilocybin. The results confirm that non-pharmacological variables play an important role in the effects of psilocybin