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R A Frank

Publications and source records attributed to R A Frank.

At least 19 recordsLinked to original sources
PubMed1996

Preclinical characterization of the potential of the putative atypical antipsychotic MDL 100,907 as a potent 5-HT2A antagonist with a favorable CNS safety profile.

In preclinical studies, [R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4- piperidinemethanol] [formula: see text] (MDL 100,907), a putative atypical antipsychotic, was characterized in vitro as a potent and selective ligand for the serotonin2A (5-HT2A) receptor and was evaluated in vitro and in vivo as a potent 5-HT2A receptor antagonist. Furthermore, MDL 100,907's potential CNS safety profile and selectivity as a potential antipsychotic agent were evaluated and compared with benchmark compounds. MDL 100,907 demonstrated low nanomolar or subnanomolar binding in vitro at the 5-HT2A receptor and showed a > 100-fold separation from all other receptors measured. MDL 100,907 had subnanomolar potency as a 5-HT2A antagonist in vitro in reversing 5-HT-stimulated inositol phosphate accumulation in NIH 3T3 cells transfected with the rat 5-HT2A receptor. In vivo, MDL 100,907 potently inhibited 5-methoxy-N, N-dimethyltryptamine-induced head twitches in mice or 5-hydroxytryptophan-induced head twitches in rats. In vivo functional tests in mice revealed a > 500-fold separation between doses that produced 5-HT2A antagonism and doses that produced alpha 1-adrenergic or striatal D2 antagonism. Using inhibition of D-amphetamine-stimulated locomotion in mice as a measure of potential antipsychotic efficacy, MDL 100,907 showed a superior CNS safety index relative to the reference compounds, haloperidol, clozapine, risperidone, ritanserin, and amperozide, in each of five tests for side effect potential, including measures of ataxia, general depressant effects, alpha 1-adrenergic antagonism, striatal D2 receptor antagonism, and muscle relaxation. MDL 100,907 did not antagonize apomorphine-induced stereotypes in rats, suggesting that it potentially lacks extrapyramidal side effect liability. MDL 100,907 showed selectivity as a potential antipsychotic in that it lacked consistent activity in selected rodent models of anticonvulsant, antidepressant, analgesic, or anxiolytic activity. In summary, these preclinical data indicate that MDL 100,907 is a potent and selective ligand at the 5-HT2A receptor. MDL 100,907's potent 5-HT2A antagonist activity might account for its activity in preclinical models of antipsychotic potential. Ongoing clinical evaluation with MDL 100,907 will test the hypothesis that 5-HT2A receptor antagonism is sufficient for antipsychotic activity in humans.

Animals↗
PubMed1995

The contribution of psychological and sensory factors to food preference patterns as measured by the Food Attitudes Survey (FAS).

The relationship between food preference patterns and several psychological and sensory variables was assessed using the Food Attitudes Survey (FAS). Previous research with the FAS, which consists of preference ratings for a variety of common, unusual and fictitious foods, showed that it provides both reliable and valid information about individual differences in food preferences and attitudes (Frank & van der Klaauw, 1994). In the studies reported here, significant correlations were found between preferences for a variety of activities (as measured by the Activity Attitudes Survey or ACT) and liking for and willingness to try foods, It was also found that individuals who report that they are unwilling to try many foods are low in general sensation seeking, and that odor pleasantness ratings significantly correlate with liking for and willingness to try foods. No associations were found between FAS performance and general phobic tendencies, optimism/pessimism or disordered eating. Multiple regression analysis revealed that responses on the ACT, sensation seeking scale, a 20-item food and eating questionnaire and odor pleasantness judgments could account for from 41 to 65% of the variance in food likes, dislikes and willingness to try foods. It was concluded that personality and sensory factors contribute to pattern of responding on the FAS, and that FAS response patterns provide an index of both attitudes toward foods and general openness to experiences and activities.

Adolescent↗
PubMed1995

Mixed D2/5-HT2A antagonism of amphetamine-induced facilitation of brain stimulation reward.

Recent experiments have demonstrated that 5-HT2A antagonists can modify electrophysiological, neurochemical, and behavioral responses to psychostimulants. These findings led to an interest in using 5-HT2A antagonists to block the effects of psychostimulants on brain reward mechanisms. The present experiments assessed the ability of mixed D2/5-HT2A antagonists to reverse amphetamine-induced facilitation of self-stimulation. The D2/5-HT2A antagonists MDL 28,133A and risperidone attenuated the effects of cocaine and amphetamine, but only at antagonist doses that elevated baseline self-stimulation thresholds. A comparison of the effects of the mixed antagonists to those of haloperidol and eticlopride revealed that all four antagonists produced similar anti-stimulant effects when the influence of the drugs on baseline responding was considered. The D2 activity of the antagonists appears to account for their ability to reduce the effects of psychostimulants on self-stimulation. 5-HT2A antagonism makes a negligible contribution to the anti-amphetamine effects.

Amphetamine↗
PubMed1994

The contribution of chemosensory factors to individual differences in reported food preferences.

A new psychometric instrument, the Food Attitude Survey (FAS), was developed to identify individual differences in general response patterns or attitudes toward foods. The FAS consists of food preference ratings (like, neutral, dislike, never tried but would try, never tried and won't try) for 455 foods and beverages, including some unusual and fictitious foods. In addition, it includes a 20-item questionnaire concerning attitudes toward food and eating. Using the FAS, people who reported liking an unusually high number of foods (likers) were compared to those who disliked many foods (dislikers) and those who were unwilling to try many foods (won't tryers). The characteristics of the three groups were evaluated using several sensory tests to assess the contribution of perceptual factors to individual differences in food attitudes and preferences. Intensity and hedonic ratings of olfactory stimuli were generally lower for the won't tryers than for the likers, with dislikers in between. In addition, the ideal taste intensities of likers were higher than those of dislikers or won't tryers. On the basis of these initial studies, it is concluded that the FAS provides a reliable index of individual differences in food preference patterns, making the FAS a useful tool for investigating the "personality of eating". The present studies also provide evidence that differences in chemosensory responses may be associated with biases toward food acceptance or rejection.

Adult↗
PubMed1994

Reoperative coronary artery bypass grafting.

In recent years reoperative coronary artery bypass surgery has become increasingly more commonplace. This article reviews the current status of this procedure with regard to patient population, risk factors, and long-term follow-up. Important aspects of the specific technical considerations involved in reoperative surgery are also reviewed and evaluated.

Coronary Artery Bypass↗
PubMed1994

Determinants of stability in the perception of subjective contours.

The present study constituted an initial experimental effort to examine the fragmentation characteristics of subjective contours within the photopic and upper scotopic ranges of illumination. Four stimulus factors known to influence the visibility of subjective contours-target luminance, inducing area size and contrast, and contour orientation--were examined. Results indicated that subjective contours are indeed unstable perceptual phenomena. On the average, fragmentation or fading occurred after only 15 sec of observation, and some form of stimulus outage was present for 28% of the viewing time of each stimulus. Fragmentation latency was significantly shorter and total time in fragmentation longer for diamond than for square contours, and total time in fragmentation varied inversely with inducing-area size. Fragmentation tended to occur in whole units rather than in isolated elements, a result reminiscent of the fading of real contours under impoverished viewing conditions.

Form Perception↗
PubMed1993

Adams-Oliver syndrome: cutis marmorata teleangiectatica congenita with multiple anomalies.

A 1-year-old female with the following multiple congenital anomalies is described: large vascular plaques on the scalp with atrophy and ulcerations, cutis marmorata and dilated veins on the trunk and extremities, short toes with partially missing phalanges and nails, retro- and micrognathia, strabismus convergens and atrial septal defect. These anomalies are characteristic of the Adams-Oliver syndrome, a rare autosomal dominant neuroectodermal syndrome which may be a maximal variant of van Lohuizen's syndrome (cutis marmorata teleangiectatica congenita).

Abnormalities, Multiple↗
PubMed1993

Both perceptual and conceptual factors influence taste-odor and taste-taste interactions.

Observers are often asked to make intensity judgments for a sensory attribute of a stimulus that is embedded in a background of "irrelevant" stimulus dimensions. Under some circumstances, these background dimensions of the stimulus can influence intensity judgments for the target attribute. For example, judgments of sweetness can be influenced by the other taste or odor qualities of a solution (Frank & Byram, 1988; Kamen et al., 1961). Experiments 1 and 2 assessed the influence of stimulus context, instructional set, and reference stimuli on cross-quality interactions in mixtures of chemosensory stimuli. Experiment 1 demonstrated that odor-induced changes in sweetness judgments were dramatically influenced when subjects rated multiple attributes of the stimulus as compared with when they judged sweetness alone. Several odorants enhanced sweetness when sweetness alone was judged, while sweetness was suppressed for these same stimuli when total-intensity ratings were broken down into ratings for the sweetness, saltiness, sourness, bitterness, and fruitiness of each solution. Experiment 2 demonstrated a similar pattern of results when bitterness was the target taste. In addition, Experiment 2 showed that the instructional effects applied to both taste-odor and taste-taste mixtures. It was concluded that the taste enhancement and suppression observed for taste-odor and taste-taste mixtures are influenced by (1) instructional sets which influence subjects' concepts of attribute categories, and (2) the perceptual similarities among the quality dimensions of the stimulus.

Adult↗
PubMed1992

Cocaine euphoria, dysphoria, and tolerance assessed using drug-induced changes in brain-stimulation reward.

The time course of cocaine-induced changes in self-stimulation thresholds were used to evaluate cocaine euphoria and dysphoria as a function of the chronicity of drug treatment, dosage level, and the spacing of injections. It was assumed that cocaine-induced decreases in thresholds were indicative of cocaine euphoria, while increases in thresholds reflected rebound dysphoric responses to cocaine administration. Three experiments were performed using self-stimulating rats implanted with ventral tegmental area electrodes. Cocaine's threshold-lowering effects were evident 15 min postinjection (IP) with thresholds returning to baseline by approximately 3.0 h after treatment. Little evidence for cocaine-induced increases in thresholds was observed during periods of chronic cocaine treatment. However, thresholds were slightly elevated upon withdrawal from chronic cocaine treatment in Experiments 2 and 3. No evidence of tolerance or sensitization to cocaine-induced shifts in thresholds was noted with single daily injections, while multiple daily injections produced tolerance to cocaine's threshold-lowering effects. It is concluded that cocaine's ability to enhance brain-stimulation reward is highly reliable and robust, while decreases in brain-stimulation reward associated with chronic cocaine treatment are less reliable and difficult to demonstrate. The possible influence of drug dosage on the induction of cocaine dysphoria and the ability of various self-stimulation procedures to measure dysphoric effects are discussed.

Animals↗
PubMed1991

Cocaine's effects on rate of intracranial self-stimulation.

While some investigators have reported that cocaine increases response rates for brain stimulation reward, others have failed to demonstrate this effect. The present study was designed to evaluate the influence of stimulation parameters, dose of cocaine and operant-dependent response requirements on cocaine's ability to alter self-stimulation rates. Self-stimulation rates were collected on a minute by minute basis for 45 min following IP injections of 0, 5, 15 or 30 mg/kg cocaine HCI. All doses were tested using both nose-poking and lever-pressing operants. It was found that mean lever-pressing rates were significantly increased by 5 mg/kg cocaine, while nose-poking rates were significantly increased by 15 and 30 mg/kg cocaine. Further examination of the pattern of results indicated that the cocaine-induced increases in lever-pressing rate were mainly due to an increase in the time spent self-stimulating, whereas increases in nose-poking were mainly due to increases in nose-poking rate/min within self-stimulation bouts. It was hypothesized that 5 mg/kg cocaine increased lever-pressing by producing response perseveration, while the higher doses increased nose-poking mainly due to the compatibility of the nose-poking response topography with cocaine-induced stereotypies.

Animals↗
PubMed1991

Effects of thyroid status and fasting on hepatic metabolism of apolipoprotein A-I.

Metabolism of apolipoprotein (apo)A-I was studied in normal and chow-fed hyperthyroid rats, in 24-h fasted untreated male rats, and in rats after thyroparathyroidectomy (TXPTX). Rats were made hyperthyroid by administration of T3 (9.6 micrograms/day) or T4 (30 micrograms/day) with an Alzet osmotic minipump. Hyperthyroidism produced a similar two- to threefold elevation in plasma levels of apoA-I in male or female animals. During treatment with T3, plasma levels of T3 ranged from 200 to 400 ng/dl and did not correlate with plasma apoA-I levels. The net mass secretion and synthesis ([3H]leucine incorporation) of apoA-I by perfused livers from male hyperthyroid rats was elevated, while secretion of albumin was not different than that of euthyroid rats. Furthermore, the incorporation of [3H]leucine into total perfusate and hepatic protein was not altered by hyperthyroidism. The effect of thyroid hormone on apoA-I synthesis, therefore, does not appear to be a general effect on protein synthesis. After longer periods of treatment (28 days) with T3 (9.6 micrograms/day), hepatic apoA-I production decreased from that observed after 7 or 14 days of treatment, yet plasma apoA-I concentrations remained elevated. Plasma T3 decreased from 100 ng/dl to 40 ng/dl, in the hypothyroid rat resulting from TXPTX, but the plasma concentration of apoA-I did not change during the 2-week experimental period. The net secretion of apoA-I by livers from hypothyroid animals was depressed and albumin was uneffected compared to the euthyroid. Overnight fasting of euthyroid rats did not alter hepatic apoA-I secretion or plasma apoA-I levels, although under fasting conditions we had reported that hepatic output of apoB and E of VLDL is depressed. The addition of oleic acid to the perfusion medium, sufficient to stimulate VLDL production, did not affect net hepatic secretion of apoA-I by livers from euthyroid, hyperthyroid, or hypothyroid rats. In summary, hepatic synthesis of apoA-I appears to be controlled independently of other apo-lipoproteins and secretory proteins (albumin). Hepatic apoA-I synthesis is sensitive to thyroid status, increased in the hyperthyroid and decreased in the hypothyroid state. The specific stimulation of hepatic synthesis and secretion of apoA-I in the hyperthyroid state, however, tends to normalize over an extended period, perhaps from compensatory effects of a hormonal nature.

Animals↗
PubMed1990

Cocaine facilitates prefrontal cortex self-stimulation.

It has been demonstrated that cocaine HCl lowers thresholds for and increases rates of medial forebrain bundle intracranial self-stimulation. The influence of cocaine on prefrontal cortex self-stimulation was assessed in the present experiment. The prefrontal cortex was chosen because evidence indicates that the neuroanatomical and pharmacological substrate for intracranial self-stimulation at this site may differ from the substrate for medial forebrain bundle self-stimulation. Cocaine significantly decreased train-duration thresholds and increased the rate of prefrontal cortex self-stimulation. It was concluded that cocaine facilitates both prefrontal cortex and medial forebrain bundle self-stimulation, perhaps by influencing neural activity in the mesocorticolimbic dopamine system. However, the role of dopamine in cocaine's effects at both sites remains speculative.

Animals↗
PubMed1989

Chronic imipramine does not block cocaine-induced increases in brain stimulation reward.

Self-stimulating rats implanted with ventral tegmental area electrodes were tested with 15 mg/kg cocaine HCl before and after chronic imipramine treatment. Chronic imipramine had no influence on cocaine's ability to lower brain stimulation reward thresholds, suggesting that tricyclic antidepressant treatment does not block cocaine-induced euphoria.

Animals↗
PubMed1988

The effect of chronic cocaine on self-stimulation train-duration thresholds.

The effect of chronic cocaine treatment on brain stimulation reward was assessed by examining self-stimulation train-duration thresholds. Following a predrug, saline injection period, cocaine hydrochloride (10 or 15 mg/kg) was injected (IP) across 18 consecutive days of testing. Cocaine lowered thresholds across the entire period of drug administration, with the magnitude of cocaine's effect remaining stable during this time. The subjects returned to predrug, saline levels during a postdrug test conducted immediately following chronic cocaine treatment. In a final attempt to modify cocaine's effects, the subjects received 25 mg/kg cocaine HCl three times/day for three consecutive days. Subsequent testing at the original dosage levels revealed no change in the magnitude of cocaine's effect. It was concluded that cocaine's effect on brain stimulation reward does not show tolerance or sensitization with chronic use. Similar effects have been reported for morphine and amphetamine's effect on brain stimulation reward.

Animals↗
PubMed1988

The interactive effects of cocaine and imipramine on self-stimulation train-duration thresholds.

The present experiment examined the ability of the tricyclic antidepressant imipramine to influence cocaine's effect on intracranial self-stimulation. Following a predrug, saline injection period, cocaine hydrochloride (10, 20 or 30 mg/kg) was injected (IP) in 19 rats implanted with ventral tegmental area electrodes. Cocaine treatment uniformly decreased self-stimulation train-duration thresholds. In the next phase, the subjects were divided into two groups. One group received cocaine (as in the previous phase) and the other received cocaine plus imipramine (10 mg/kg, IP). Imipramine doubled cocaine's effect on self-stimulation train-duration thresholds. In addition, several other effects of cocaine (e.g., bradycardia, rear-limb dyskinesia) were potentiated by imipramine treatment. The results suggest that care must be exercised when treating cocaine abuse with tricyclic antidepressants since coadministration of these drugs intensifies cocaine's effects.

Animals↗
PubMed1987

The effect of operant and electrode placement on self-stimulation train duration response functions.

Multiple operants have been used to assess the effects of drugs on self-stimulation. It has typically been assumed that changing the operant used to obtain brain stimulation represents a simple performance manipulation. However, the validity of this assumption has been challenged by several research findings. The present study sought to clarify the role of response topography and slight differences in electrode placement on operant-induced shifts in self-stimulation thresholds and response rates. Thresholds and rates were determined for three operants (leverpressing, nosepoking and omnidirectional leverpressing) using two bilaterally placed electrodes. In addition, the response topographies used to perform each operant were evaluated. It was found that the relationship between the thresholds and rates produced by the operants was more dependent on the electrode placement than operant or subject-specific factors. The results of this experiment suggest that the characteristics of the stimulation site determine the relationship among different operants. This finding may be due to differences in the reward substrate or stimulation-induced behaviors activated at various brain loci.

Animals↗