Attention as a target of intoxication: insights and methods from studies of drug abuse.

A symposium was convened to discuss recent developments in the assessment of attention and the effects of drugs and toxic chemicals on attention at the 17th annual meeting of the Behavioral Toxicology Society on May 1, 1999, in Research Triangle Park, NC. Speakers addressed issues including the methodology of assessing cognitive function, the neurobiology of specific aspects of attention, the dual roles of attention as a target of intoxication and as a mediating variable in the development of addiction to psychoactive drugs, the changes in attention that accompany neuropsychological disorders of schizophrenia, senile dementia of the Alzheimer type and attention deficit hyperactivity disorder, and potential therapies for these disorders. This article provides an overview of the objectives of the symposium, followed by summaries of each of the talks given.

Food intake in Prader-Willi syndrome and controls with obesity after administration of a benzodiazepine receptor agonist.

Benzodiazepine receptor (BZR) agonists, used extensively for their anxiolytic effects, have been shown to increase food intake in many mammalian species. Little information, however, is available on the effects of BZR agonists on feeding behaviors of humans. Food intake was evaluated in a 60-minute free-feeding standardized test after the acute administration of the BZR agonist chlordiazepoxide (CDP, Librium; 5 mg or 20 mg) or placebo. Subjects were 12 individuals with the Prader-Willi syndrome (PWS), a disorder characterized by extreme hyperphagia and morbid obesity, and 11 controls with obesity. PWS subjects showed the characteristic hyperphagia associated with the appetite disorder, consuming more than six times as many sandwiches as controls with obesity. Results revealed no significant effect of either dose of CDP on the food intake of either group. Serum assays revealed that dose-dependent, clinically effective levels of CDP and active metabolites were achieved. These results suggest that acute administration of the BZR agonist CDP, at the therapeutic levels used, may not increase food intake in populations with obesity. However, the chronic effects of CDP on appetite in human populations still need to be explored.

Cognitive functions of cortical ACh: lessons from studies on trans-synaptic modulation of activated efflux.

Trans-synaptic modulation of cortical ACh efflux is a useful approach for determining the functions of cortical ACh. Bilateral modulation of basal forebrain GABAergic transmission by benzodiazepine-receptor agonists and inverse agonists decreases and increases, respectively, activated cortical ACh efflux. The determination of behavioral functions which are mediated via activated cortical ACh efflux, and therefore subject to the effects of basal forebrain GABA-cholinergic manipulations, should promote analyses of the functions of cortical ACh. Trans-synaptic approaches to enhance activated cortical ACh efflux offer some potential for the treatment of cognitive dysfunctions associated with impaired cortical cholinergic transmission.

Cardiovascular effects of the benzodiazepine receptor partial inverse agonist FG 7142 in rats.

Effects of the benzodiazepine receptor (BZR) partial inverse agonist FG 7142 (FG) on basal and reactive cardiovascular measures were examined in freely moving rats. FG (8 mg/kg) modestly increased basal heart period, but had no effects on basal blood pressure. More notably, however, FG augmented the cardioacceleratory response to an auditory stimulus relative to vehicle controls. Selective blockade of sympathetic (atenolol, 1 mg/kg) or parasympathetic (scopolamine methylnitrate, 0.1 mg/kg) effects on the heart under control conditions revealed that the stimulus-evoked cardiac response originated from a concurrent (reciprocal) sympathetic activation and vagal withdrawal. Following FG pretreatment, both atenolol and scopolamine blocked the cardioacceleratory response to the auditory stimulus. Thus, although FG minimally increased basal heart period, FG significantly enhanced a reactive cardioacceleration. More importantly, these results demonstrate that the cardiovascular effects of BZR inverse agonists are more fully characterized by an assessment of both tonic and reactive cardiovascular responses.