Residual effects of ecstasy (3,4-methylenedioxymethamphetamine) on low level visual processes.

'Ecstasy' (3,4-methylenedioxymethamphetamine) induces impaired functioning in the serotonergic system, including the occipital lobe. This study employed the 'tilt aftereffect' paradigm to operationalise the function of orientation-selective neurons among ecstasy consumers and controls as a means of investigating the role of reduced serotonin on visual orientation processing. The magnitude of the tilt aftereffect reflects the extent of lateral inhibition between orientation-selective neurons and is elicited to both 'real' contours, processed in visual cortex area V1, and illusory contours, processed in V2. The magnitude of tilt aftereffect to both contour types was examined among 19 ecstasy users (6 ecstasy only; 13 ecstasy-plus-cannabis users) and 23 matched controls (9 cannabis-only users; 14 drug-naive). Ecstasy users had a significantly greater tilt magnitude than non-users for real contours (Hedge's g = 0.63) but not for illusory contours (g = 0.20). These findings provide support for literature suggesting that residual effects of ecstasy (and reduced serotonin) impairs lateral inhibition between orientation-selective neurons in V1, which however suggests that ecstasy may not substantially affect this process in V2. Multiple studies have now demonstrated ecstasy-related deficits on basic visual functions, including orientation and motion processing. Such low-level effects may contribute to the impact of ecstasy use on neuropsychological tests of visuospatial function.

Cholinergic agents and the McCollough effect.

The strength of the McCollough effect (ME), a pattern-contingent colour aftereffect, has been shown to be inversely related to acetylcholine, being significantly strengthened by (anticholinergic) scopolamine and weakened by (cholinergic) physostigmine delivered before adapting to the ME stimuli. The purpose of the present study was (i) to establish whether the effect of pre-adaptation scopolamine is linearly dose-dependent and (ii) to investigate the effects of scopolamine and physostigmine delivered between adaptation and testing. In experiment 1, ten healthy male volunteers who received placebo, or 0.6 mg, 1.2 mg, or 1.8 mg scopolamine before adapting to ME stimuli showed a significant linear dose-dependence over tests repeated from 10 to 70 min after adaptation. In experiment 2 twelve male volunteers adapted to ME stimuli and then received placebo, 1.2 mg oral scopolamine, or 0.75 mg subcutaneous physostigmine. On subsequent repeated testing, strength of the ME was increased by scopolamine and decreased by physostigmine relative to placebo. Both experiments were double-blind double-dummy repeated measures. These data support the view that the ME is a product of inhibitory mechanisms in the visual system rather than processes involved in associative learning.

Visible persistence decay rates for schizophrenics and substance abusers.

Information-processing deficits are consistently reported for schizophrenics. The findings from the majority of psychophysical tasks indicate that the deficit is specific to schizophrenics and thus may represent a marker for schizophrenia. The present study evaluated for specificity of impairment by including controls using methadone. A two-pulsed forced choice information-processing task that required the detection of a line or a blank-field during an interstimulus interval (ISI) indexed efficiency of processing (i.e., visible persistence). There were 19 schizophrenic, 9 schizoaffective, 8 depressed, 12 on methadone, and 12 normal subjects. The visual stimuli were low and high spatial frequency gratings. Either a line of equivalent width to those of the gratings or a blank field was presented during the ISI. The gratings were presented for 150 msec prior to and following an ISI of 30, 60, 90, 120, 150, and 350 msec. The results support previous findings for impaired processing during a 90-150 msec interval for schizophrenics. Also, the methadone-using controls were not significantly different from schizophrenics. Normal and depressed controls' profiles did not differ from each other, however, they were significantly different from the other groups. The results support an early information-processing deficit in schizophrenic individuals and may implicate dysregulation of dopaminergic neuromodulation.

The McCollough effect as a measure of central cholinergic activity in man.

The McCollough Effect (ME) is an orientation contingent colour after-effect which has been proposed as an indicator of central neurotransmitter activity. Shute (1979) suggested that the ME could reflect a hippocampal "forgetting" mechanism which should be inhibited by GABAergic neurones and stimulated by cholinergic neurones. The purpose of the present study was to demonstrate that the ME is in fact sensitive to cholinergic and anticholinergic drugs and to compare its sensitivity to more conventional tests of psychomotor and cognitive function. Ten healthy subjects received single doses of physostigmine (0.75 mg SC), hyoscine (1.2 mg), temazepam (20 mg), flecainide (200 mg) or placebo in a double-blind double-dummy presentation. Subjects were tested on a battery of psychomotor and cognitive function tests at baseline and 1 h, and adapted to the ME at 1.5 h. Visual analogue rating scales and conventional tests of psychomotor function and saccadic eye movements indicated that both subjective and objective measures of arousal were impaired by temazepam. The subjective, but not the objective, measures of arousal were also impaired by both hyoscine and physostigmine, but not by flecainide. Initial strength and duration of the ME were decreased by physostigmine and increased by hyoscine and temazepam, relative to placebo (P less than 0.01). Thus, the ME is capable of detecting cholinergic, anticholinergic and GABA mimetic drug effects in man, in therapeutic doses.

Tilt aftereffect reveals early visual processing deficits in Parkinson's disease and in chronic schizophrenic patients on depot neuroleptic.

Previous studies suggest that the tilt aftereffect (TAE) may be used to indicate the site of dopaminergic abnormalities in the human visual system. In this study we investigated the TAE in patients with Parkinson's disease, and in chronic schizophrenic patients receiving depot injections of neuroleptic. The results suggest that the retina may be abnormal in both groups of patients, and that schizophrenic patients may also have cortical changes. The results are discussed in terms of the clinical implications of these visual changes.

Behavioral effects of 0 and 0.05% blood alcohol in male volunteers.

Five behavioral tests were evaluated to determine their sensitivity to the subtle central nervous system (CNS) depressant effects produced by ingestion of ethanol. Twenty-one adult male volunteers received 0 and 1.4 ml 100 proof vodka/kg body weight according to a "double-blind" crossover design. Behavioral tests were conducted between 15 and 65 minutes after ethanol ingestion, when blood alcohol concentrations (BAC's) were between 0.05 and 0.06%. Tests evaluated were Archimedes spiral, digit span memory, critical flicker fusion, stabilometry and tachistoscope. Multivariate analysis of variance (MANOVA) using composite scores representing the individual tests indicated that the battery as a whole was sensitive to ethanol effects. Repeated measures analysis of variance (ANOVA) on each test indicated that critical flicker fusion, stabilometry and tachistoscope contributed more to the overall sensitivity of the battery than did digit span memory and Archimedes spiral.

Classification and determination of cerebral bioavailability of fluoxetine: pharmacokinetic, pharmaco-EEG, and psychometric analyses.

In a double-blind placebo-controlled cross-over study, the pharmacokinetic, encephalotropic, and psychotropic properties of fluoxetine were investigated in 8 normal volunteers. Subjects received in randomized order, at 2-week intervals, single oral doses of placebo and 30, 60, and 75 mg of fluoxetine. Data were obtained at baseline and 2, 4, 6, 8, and 10 hours after drug administration. There was a dose-dependent rise in plasma levels up to the 4th to 6th hour, followed by a slow decline, consistent with the reported long half-life. Digital computer period EEG analysis showed only mild encephalotropic effects of fluoxetine compared with placebo. The EEG changes, especially in the vigilance-controlled recordings, were similar to those seen after antidepressants of the desipramine type; changes in resting EEGs after the highest dose resembled those seen after imipramine-like drugs. Maximal CNS efficacy occurred between the 8th and 10th hours postdrug. The hysteresis between peak blood levels and maximal pharmacodynamic effects suggests formation of an active metabolite. Psychometric investigations showed behavioral changes after fluoxetine that are known to occur after the administration of antidepressants to normal subjects. The drug was well tolerated.