Event-related potentials and selective auditory and visual attention in autism

P.3 Psychotic disorders and antipsychotics which pseudorandomly appear at the left or the right ear. Stimuliconsist of two types: standard stimuli with an occurrencerate of 80% and deviant stimuli with an occurrence rate of 20%, with a probability of 50% for each ear. In this way 150 tones are presented to each ear. Subjects are instructed to attend only to the rare stimuli (targets) at one ear. The visual task follows a similar procedure. Stimuli are 300 red and yellow rectanglesfilled with leftward ( ) or rightward (If) oriented diagonal gratings. All stimuli are presented in the center of the visual field and stimuli are distributed within and between channels in the same way as in the auditory task. Subjects are instructed to react as fast as possible to rectangles of one color with deviantgrating orientations. Two processing steps are required in such a task. First, the relevant charmel has to be selected, and next the target has to be identified within that channel. In the ERP, the latter step is reflected by the P300 and the first step is reflected by an earlier wave, the so-called Processing Negativity (PN). During the selective attention tasks we are measuring ERPs at 64 electrodes. This enables us to locate in the brain electrical dipoles which produce the measured ERP waves. As expected, in a pilot of these procedures with adult volunteers, we found a larger Processing Negativity for the attended channel and larger P300s for target stimuli. The results of the dipole estimations will be presented. References Jonkman, LM., Kemner, C., Koelega,H.S., v.d.Gaag, R.I., Buitelaar J.K., van Engeland H. andVerhaten, M.N. (1996) Event-related potentials and performance of ADHD children and nonnal controls inauditory and visual selective attention tasks. BioI. Psychiatry, in press. Kemner, C., Verhaten, M.N., Cuperus, J.M., Camfferrnan, G. and van Engeland, H. (1994) Visual and somatosensory event-related brain potentials in autistic children andthree different control groups. Electroenceph. clin. Neurophysiol., 77. 436-444.

Kemner. C., Verbaten, M.N., Cuperus, J.M., Camfferman, G. and van Engeland, H. (1995) Auditory event-related brain potentials in autistic children and three different control groups. BioI. Psychiatry. 38,150-165.

IP.3.0071 Lack of interaction between amisulpride and

lorazepam on psychomotor performance and memory In healthy volunteers

M.C. Perault ' , L. Bergougnan 2, A. Paillat I , C. Gomeni3, 1.Zieleniuk 2, B. Vandel ' . I Clinical Pharmacology Unit, CHU, BP 577, 86021 Poitiers Cedex; France; 2 Synthelabo Recherche, Clinical Pharmacology Section, BP 110. 92225 Bagneux Cedex, France; 3 L.eG. Simed, 9-11 rue G. Enesco, 94008Creteil, France Amisulpride (AMS) is a benzamide antipsychotic that preferentially blocks presynapticdopamine D2 and D3 receptors, in the limbicsystem. The aim of the study was to evaluate potential pharmacodynamic interactions between amisulpride and lorazepam (LZP) on psychomotor performance and cognitive functions, in 18 healthy male caucasian volunteers, aged 18 to 35 years. The cross-over randomised, double blind. placebo controlled study,included six one day single doses treatmentperiods, separatedby wash-out periodsof one week. AMS was administered at the dose of 50 mg or 200 mg and LZP at the dose of 2 mg. Pharmacodynamic evaluation criteria were for psychomotor performance. critical flicker fusion (CFF), visual reaction time (VRT) (msec), tapping, Pauli test (number of correct answers), multiplechoice reaction time (MCRn. body sway. Memory was assessed by Buschke's test (eg: number of delayed recalled words). Subjective sensationswere measured with the Addiction Research Centre Inventory (ARCI49). Prolactin assays were performed before and 3.5 h after dosing. Safety was recorded by collection of adverse events, laboratory tests and cardiovascular monitoring. The analyses were performed at each time point, using a 3 way anova (subject, period, treatment) (6 levels) with contrast partitioning the treatmentsum of squares. For psychometric tests. analyses were performed on changes from baseline. For memory test, analysesweredone on raw data. The co-administration of AMS, at both doses of 50 mg and 200 mg. did not potentiate nor antagonize the detrimental effect of UP 2 mg on pharmacodynamic parameters. AMS. at oral dose of 50 mg and 200 mg, was devoid of any clinically relevant effect on psychometric tests (CFF,

Table I. Psychometric performances and memory [est values VRT (H2) Pauli Test (H2) Placebo 195.8 ± 25.2 200.0 ± 35.5 LZP2mg 248.2 ± 56.6 150.9 ± 42.9 AMS50mg 209.6 ± 31.6 197.1 ± 38.3 LZP2 mg+AMS 50 mg 257.3 ± 60.0 15D.6 ± 36.1 AMS200mg 208.4 ± 21.2 198.8 ± 43.5 UP 2 mg+ AMS 200mg 250.2 ± 69.9 154.1 ± 55.8

S4-103

Buschke's Test 13.22 ± 2.24 8.78 ± 3.1 13.28 ± 2.65 8.06 ± 3.93 13.06 ± 2.58 8.56 ± 4.06

VRT, tapping, Pauli test, MCRT), short term and long term memory tests, and mood (ARC!). In contrast, LZP 2 mg induced significant marked impairment (p < 0.(01) in psychometric performances, which all, except CFF test, were negatively affected by UP (table I). Disturbances were also recorded in memory tests, balance (body sway) and subjective sensation (ARC!).The peale of activity was 2 to 4 hours after administration. but the majority of results was also affected up to 8 hours. Prolactin levels wereincreasedafter AMS administration (both doses), but not after placebo or LZP, while the co-administration of AMS plus LZP induced a prolactin elevation equivalent to that of AMS alone. The safety of AMS was satisfactory. No clinically relevantmodification of ECG. blood pressure or heart rate was noted and no biological values were outside clinically significant ranges. Adverses events were mainly encountered after LZP and LZP plus AMS association. In conclusion, AMS at single oral dose of 50 mg or 200 mg, did not disturb psychomotor and cognitive functions and did not interact with a single oral dose of LZP 2 mg. Therefore. the co-administration of both drugs should not be contraindicated.

I p.3.ooal

Dopaminerglc and nicotinic interactions in the human striatum in Dementia with Lewy bodies, chronic schizophrenia andParkinson's disease

M.A. Piggott,JA Court, E.K. Perry,S. Lloyd, N.J. Thomas, Z.M. Smith. M. Johnson, R.H. Perry.I.G. McKeith. MRC Neurochemical Pathology Unit, Newcastle General Hospital, Westgate Road, Newcastle-upon-Tyne, NE4 68E, UK The neuronal nicotinic receptor, responsible for high affinity nicotine binding, is likely to be involved in the control of dopamine release in the striatum. We have examined this receptor autoradiographically by [3Hj nicotine binding in the human striatum. In normal. elderly cases binding was slightly higher (1(}""20%) in the nucleus accumbens and caudatecomparedto the putamen. The normal distribution was generally patchy although variations in binding did not reflect the striosome/matrix organisation as revealed by acetylcholinesterase staining. In Parkinson's diseasethere was a significantreduction of [3Hj nicotine binding in caudate and putamen, consistent with the loss of nigrostriatal innervation, which was also reflected in the extensive reduction in [3Hj rnazindol binding to the dopamine uptake site. Dopamine D2 receptors were elevated, also in line with nigrostriatal loss. In Dementiawith Lewy bodies (DLB) [3Hl nicotine binding was moderarely reduced in cases not treated with neuroleptics. More extensive reductions, significant in all regions of the caudate and putamen, were associated with neuroleptic medication. Neuroleptic-induced nicotinicreceptor loss may.via reduceddopaminerelease, increase the probability of the development of extrapyramidal side effectswith medication,although there was no difference in [3H] nicotine binding between neuroleptic tolerant and neuroleptic sensitive groups. D2 binding tended to be lower compared to controls in neuroleptic naive DLB cases. but was elevatedin neuroleptic tolerantDLB cases (Piggott et al 1994). In a group of chronic, elderly schizophrenics, who had mainly negative symptoms and suffered from movementdisorders, [3H] nicotine binding was increased by an average of 85% compared to control cases, a finding that may relate to the high incidence of tobacco smoking in this group. Preliminary evidence comparing the schizophrenic group with·controls who were smokers suggests that this may not fully account for the elevated receptor levels. D2 receptors in striatum in this group were reducedcomparedto controls. Dopamine D2 receptorswill be investigated in normal individuals with a history of smoking or not smoking. Modulation of D2 receptors by cigarette smokingcould be an explanation for the protectiveinfluenceof