The influence of ondansetron and m-chlorophenylpiperazine on scopolamine-induced cognitive, behavioral, and physiological responses in young healthy controls.

BACKGROUND: There is evidence from animal and human experiments that learning and memory come under the separate influence of both cholinergic and serotonergic pathways. We were interested in learning whether serotonergic drugs could attenuate or exacerbate the memory-impairing effects of anticholinergic blockade in humans. METHODS: The selective serotonin 5-HT3 receptor antagonist ondansetron (0.15 mg/kg i.v.) and the serotonergic agent m-chlorophenylpiperazine (m-CPP; 0.08 mg/kg i.v.) were administered in combination with the anticholinergic agent scopolamine (0.4 mg PO) and compared to scopolamine alone in 10 young, healthy volunteers. Testing occurred on three separate days. RESULTS: As expected, i.v. administration of scopolamine induced significant impairments in episodic memory and processing speed; however, these scopolamine-induced cognitive deficits were not attenuated by pretreatment with i.v. ondansetron (0.15 mg/kg), nor were they exacerbated by administration of i.v. m-CPP (0.8 mg/kg) in addition to scopolamine; however, administration of i.v. m-CPP was followed by a significant increase of self-rated functional impairment, altered self-reality, and dysphoria ratings, and scopolamine's effect on pupil size was potentiated. CONCLUSIONS: Together, these results suggest that in young, healthy volunteers scopolamine-induced changes of cognitive performance are only minimally modulated by the serotonergic effects on ondansetron and m-CPP. Further studies with older controls are needed to test whether these findings may be influenced by age.

Distribution of peripheral lymphocytes in Alzheimer patients and controls.

Deficient immunoregulation has been postulated to play a role in the pathogenesis of Alzheimer's dementia. Recently, lymphopenia was reported to be more prevalent in Alzheimer patients than in control subjects. In addition, a decreasing number of total lymphocytes was found to be significantly correlated with increasing severity of dementia. In an attempt to replicate these findings, we studied 55 Alzheimer patients and 41 healthy controls of comparable age and gender, but found no significant difference in the distribution of total lymphocytes between these groups. Furthermore, total lymphocytes were not significantly correlated with dementia severity. Our findings, therefore, do not lend further support to an immune hypothesis for Alzheimer's dementia.

Intravenous procaine as a probe of limbic system activity in psychiatric patients and normal controls.

Evidence from animal and human studies suggests that procaine hydrochloride may selectively activate limbic system structures and suppress neocortical structures. We administered a series of intravenous bolus doses of procaine hydrochloride to 31 subjects (7 with affective disorders, 17 with borderline personality disorder, and 7 healthy normal volunteers). Dose-related cognitive and sensory distortions and illusions were observed; affective experiences ranged widely from euphoric to dysphoric. Topographic electroencephalogram (EEG) analysis indicated selective increases in fast activity (26-45 Hz) over the temporal lobes; the degree of increase in this activity correlated with degree of dysphoria experienced. Procaine was associated with increases in secretion of cortisol, adrenocorticotrophic hormone (ACTH), and prolactin, but not with growth hormone. These preliminary data are consistent with the possibility that procaine might serve as a clinically useful probe of psychosensory, affective, electrophysiological, and endocrine effects referable to the limbic system.

Motor activity in depressed patients treated with carbamazepine.

Motor activity in 19 depressed patients treated with carbamazepine was assessed using self-contained monitors worn on the wrist. Those whose depression improved demonstrated significant increases in motor activity. Nonresponders as a group did not show decreased motor activity, suggesting that carbamazepine was not producing sedation or hypoactivity at clinically relevant doses. Activity counts were negatively correlated with ratings of global severity of depression on the Bunney-Hamburg Scale and with degree of motor retardation rated on the BPRS during treatment. The selective increases in motor activity in those who improved are consistent with psychomotor changes related to amelioration of depression.

Mood-altering effects of disulfiram in alcoholics.

The effects of disulfiram on depression and anxiety were examined. In a 3-week double-blind study, 40 inpatients in al alcohol rehabilitation unit (ARU) were randomly assigned to receive placebo, 250 mg/day of disulfiram or 500 mg/day of disulfiram. During their first week in the ARU and prior to beginning medications, all subjects were administered the Zung self-rating depression scale, the Hamilton observer rating scale for depression, the Zung self-rating scale for anxiety and the Hamilton observer rating scale for anxiety. All subjects were rescored on these instruments at the end of their third week in the ARU. Three psychiatrists, blind to the medication condition, sequentially scored the Hamilton items. To evaluate intergroup differences at baseline as well as changes in scale scores during the 3 weeks, scale scores were subjected to analyses of variance. No statistically significant effect attributable to disulfiram was found but significant changes due to a time effect were noted.