P.6.007 Acute and subchronic effects of gammahydroxybutyrate (GHB) on isolation induced aggression in male mice

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Olanzapine oppositional aggressive,

treatment defiant antisocial

Other

in children with disorder (ODD) and behavior

D.H. Shawu’ , I. Shawu2. ‘Hospital for Sick Children, Toronto, Pediatrics, Toronto, Ontario, Canada; ‘University of Western Ontario, Undergraduate science, genetics majol; Toronto, Ontario, Canada

Purpose: Six prepubertal children with ODD all demoustratiug aggressive, a&social behavior were studied using au open-label trial of olauzapiue (2.555 “g/day). The children were treated with the goal of decreasing serious symptomatology aud helping the caregivers to cope. Method: All six patients met the Diagnostic aud Statistical Mauual of Meutal Disorders @SM-IV) criteria for ODD. Three also met the DSM-IV criteria for atteutiou deficit hyperactivity disorder (ADHD). In all patieuts, treatment begau with a behavior modification program, family couuseliug, aud classroom modifications. The three patients with co-morbid ADHD were also treated with a psychostimulaut aud oue of them received a trial of risperidoue. Wheu it was determiued that these iuterveutious were uot effective treatments for the children’ s ODD aud aggressive, antisocial behavior, all families chose the option of au open-label trial of olauzapiue. Pareuts were told that there is presently 110 iudicatiou for the use of olauzapiue in the treatment of ODD. Studies using olauzapiue in the treatment of children with pervasive developmental disorder aud aggressive or antisocial behavior were reveiwed. Au iuformatiou sheet outliuiug reported aud poteutial side effects of olauzapiue was provided. Gracious (2001) suggested a star&g dose of 2.5 mg olauzapiue with 2.5 mg iucremeuts every 3 to 7 days. The authors begau more couservatively with a starting dose of 1.25 mg aud slowly titrated upwards in 1.25 mg increments. Using the Clinical Global Impressions (CGI) General Scoring Sheet, a pretreatment CGI ’ Severity of Illness score was determined. The effect of olauzapiue treatment was determiued using the CGI General Scoring Sheet: post treatmeut CGI ’ Severity of Illness’ score, post treatment CGI ’ Global Improvemeiit’ score, aud post treatment CGI ’ Efficacy Index’ score. The followiug laboratory tests were followed: complete blood couut; aspartate amiuotrausferase, alkaline phosphatase, total bilirubiu; hemoglobin AlC, fasting blood glucose; electrocardiogram. It was uot necessary to exceed the lowest dosage cited in previous studies: 5-10 mg (Malone 2001) or 5-20 mg (Poteuza 1999). Results: The pretreatment CGI ‘Severity of Illness’ score was ‘5 or 6=Markedly or Severely mentally ill’ in all six patients. The post-treatment CGI ‘Severity of Illness’ score is ‘1 or 2=Not at all mentally ill or Borderliue mentally ill’ The results of the CGI ’ Global Improvement’ score are ’ Much or Very much improved’ which indicates a response to treatment. The amelioration of the aggressive, antisocial behavior appears to have made a dramatic impact 011 the quality of life for these children, their caregivers, aud school staff. The adverse effects observed included: sedation in two patients (transient), baud tremor in oue patient (trausieut), aud weight gaiu in all patients (S-34% increase). Laboratory tests remaiued uonnal in all subjects (including hemoglobin AlC aud fasting blood glucose). Conclusion: The fiudiugs suggest that olauzapiue, at low doses, may be a useful pharmacologic ageut for coutrolliug aggressive, antisocial behavior in children with ODD.

topics

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Effects of early parental divorce on young adults hypothalamic-pituitary-adrenal corticotropin releasing test

seperation due to - assessment of the axis using the hormone stimulation

M. Bloch’, I. Peleg2, D. Koreu2, E. Kleiu2. Medical Center, Psychiatry, Tel Aviv, Israel; Centel; Psychiatry, Haifa, Israel

‘Tel Aviv ‘Ran&am

Sourasb Medical

Childhood trauma may result in loug tenn alteratious in HPA axis activity that may mediate adult psychopathology. While such alteratious are well documented in auimal models aud in women survivors of childhood sexual abuse, data reflecting early pareutal loss in humaus is scarce. We investigated the loug tenn effect of early pareutal divorce 011 HPA Axis activity in adults, using a standard CRH stimulation test. Twenty two healthy males aud females (age 1 S-25) whose pareuts divorced before they reached age 10, aud 22 controls were included. All were iuterviewed using a structured iuterview (SCID) aud a demographics aud trauma questiomlaire. Exclusion criteria were major physical illuess, curreut or past psychopathology, aud siguificaut past trauma. Psychiatric symptomatology aud pareutal boudiug were assesed by self administered questiomlaires (BSI,PBI). Subjects aud controls did uot differ at baseline. ACTH levels were cousisteutly higher aud cortisol levels lower in subjects compared to controls at all time points (ANOVA ~ ns.). Cortisol level was lower in subjects at 5 minutes after CRH administration (piO.05). Wheu the groups were reaualysed while excluding subjects with high baseline ACTH (11=27), a significant group X time effect was observed for cortisol (F5,21=3.4; p=O.O22). Our data suggest that children experieuciug early divorce of their pareuts may have louglastiug effects 011 the HPA axis, which may be either the result of marginal psychopathology or, alteruatively, make them predisposed to developiug psychopathology later in life. However, the effect found is small aud may be biased by the selection of “super healthy” subjects. This effect aud the effect of iuterveuiug factors should be further studied.

I P6.007

Acute and subchronic gammahydroxybutyrate induced aggression

effects of (GHB) on isolationin male mice

J.F. Navarro, F. Gonzalez, C. Pedraza. Faculty of Psychology. University of Mlaga, Department of Psychobiology, Mcilaga, Spain Gammahydroxybutyrate (GHB) is a uew drug with abuse poteutial popularly knowu as “liquid ecstasy”. It is au eudogeuous compound of the mammalian brain, syuthesized from GABA, which cau traverse the blood-brain barrier. The presence of braiu receptor sites as well as braiu mechanisms for syuthesis, release, aud uptake provides evidence that GHB may act as a ueuromodulator 011 specific ueuroual populations. In this sense, there are experimental data suggesting the existence of a central iuteractiou betweeu GHB aud dopamiue receptor (1). This study was designed to assess the effects of low (5 mgkg) aud high doses of GHB (25, 75, 100 mgikg), acutely or subchrouically administered for 15 consecutive days, 011 isolation-induced aggression in male mice, using au ethophannacological approach. Albino adult male mice of the OF. 1 straiu were used. Animals were randomly allocated to oue control group (N=12) receiving physiological saliue aud eight

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experimental groups (I+11 each) receiving acute or subchrouic doses of GHB (55100 mgkg, ip). Individually housed mice were exposed to auosmic “standard oppoueuts” 30 miu after drug administration Teu miu of diadic iuteractious were staged betweeu a singly housed aud au auosmic mouse in a neutral area. The eucouuters were videotaped aud the accumulated time allocated by subjects to teu broad behavioural categories was estimated using au ethologically based analysis. The names of categories were as follows: 1. Body care; 2. Digging; 3. Nou social exploration; 4. Exploratiou from a distauce; 5. Social iuvestigatiou; 6. Threat; 7. Attack; 8. Avoidance/flee; 9. Defeuseisubmissiou; 10. Immobility. As statistical analysis, uouparametric KruskalWallis aud Mamln-Whituey U-tests were used. As compared with the control group, acute treatment with GHB (25, 50 aud 100 mgkg) provoked a significant reduction of offensive behaviours (threat aud attack) without affecting immobility, whereas with the lowest dose used (5 mgkg) a siguificaut iucrease of these behaviors was observed (piO.05). This behavioral profile was maiutaiued wheu GHB (255100 mgkg) was administered during 15 consecutive days, suggesting au absence of tolerance to the initial autiaggressive action of the drug. However, the subchrouic treatment with 5 mgkg of GHB produced au opposite effect to that observed after single treatment, suggesting a possible deseusitizatiou of postsiuaptic dopamiuergic receptors. In conclusion, it is proposed that low doses of GHB (5 mgkg) could exert their effects by biudiug to high affinity receptors, thus provokiug au iucrease in dopamiue releasing, responsible for the iucreased offensive behaviours of mice. On the other baud, higher doses of GHB (255100 mgkg) could produce a reduction of dopamiue releasing and, cousequeutly, a decrement of aggression In fact, it has beeu proposed that GHB exhibits au autidopamiuergic aud ueuroleptic-like activity in agouistic eucouuters betweeu male mice (2).

topics (1). Most typical ueuroleptics ageuts are effective autiaggressive ageuts (2, 3). However, to date, there is uo iuformatiou with respect to the possible effects of sigma-l ligauds ou aggressive behaviour in laboratory animals. Therefore, the aim of this study was to examine the effects of acute treatment with SKF 10047 (0.5, 1, 2, 4, 6 aud 8 mgkg, ip), a classical sigma-l selective agonist, or saline, ou isolation-induced aggression in male mice, using au ethopharmacological approach. This procedure permits to evaluate realiably whether the autiaggressive action of a giveu drug is specific or nonspecific. Individually housed mice were exposed to auosmic “standard oppoueuts” 30 miu after drug administration Teu miu of diadic iuteractious were staged betweeu a singly housed aud au auosmic mouse in a neutral area. The eucouuters were videotaped aud the accumulated time allocated by subjects to teu broad behavioural categories was estimated using au ethologically based analysis. The names of categories were as follows: 1. Body care; 2. Digging; 3. Nou social exploration; 4. Exploratiou from a distance; 5. Social iuvestigatiou; 6. Threat; 7. Attack, 8. Avoidauceiflee; 9. Defeuseisubmissiou; 10. Immobility. As statistical analysis, uouparametric Kruskal-Wallis aud Maml-Whituey U-tests were used. SKF 10047 (6 mgkg) produced a significant reduction of attack behavior, as compared with the control group (piO.05). No significant differences were found betweeu experimental aud control groups in the rest of the behavioural categories aualyzed. Further studies are ueeded to co&inn the possible implication of sigma receptors in aggressive behaviour. References [l] Bowen, [2] Navarro, [3] Navarro, atry, 24,

W.D. (2001). Pharmac Acta Helv, 74, 211 l-8. J.F. et al (1993). Physiol. Behav., 53, 1055-9. J.F. et al (2000). Progr. NeulroPsychopharlnacol.

Biol. Psychi-

13142.

References [l]

Navarro JP et al. (1998). Prog. NeuroPsychopharlnacol. Biol. Psychiatry, 22, 83544. [2] Navarro JF, Pedraza C. (1996). Med. Sci. Res., 24, 817-9

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D. Belt&, University Spain

An ethopharmacological assessment of the effects of SKF 10047. a sigma-l selective agonist, on social in&actions between male mice M. Cavas, of MLilaga,

J.F. Navarro. Department

Faculty of Psychology. of Psychobiology, MLilaga,

Although the sigma biudiug site was iuitially described as a subtype of opiate receptor, subsequent studies led to reclassification of these biudiug sites as unique entities. The sigma-l receptor, localized iutracelularly withiu ueurous, is a 223-aminoacid protein cloued in several auimal species aud humans. Its regional distribution indicates moderate to iuteuse staiuiug in most of the dopamiuergic structures. From a behavioural point of view, sigma-l receptors have beeu implicated in cocaine‘s rewardiug effects aud the motivational actions of ethanol. Furthermore, sigma receptor ligauds exhibit auxiolytic (auti-stress), auti-amnesic, autidepressaut aud ueuroprotective effects. Sigma receptors are high affinity biudiug sites for mauy drugs with psychotropic activity. Thus, both sigma-l aud sigma-2 receptors exhibit high to moderate affinity for typical ueuroleptics, such as haloperidol

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009

S. Uguz’ Medicine, Psychiatry,

Possible psychosocial sexual dysfunctions A descriptive study

of

, M.L. Soylu2. ‘Cukurova Psychiatry, Adana, Turkey; Adana, Turkey

factors Turkish

for males:

University ‘Adana

Faculty of State Hospital,

This paper describes the demographic characteristics, related factors, aud clinical symptomatology of 40 male patients with various sexual dysfuuctious atteudiug the psychiatric outpatient cliuic of Cukurova University, in Turkey. Method: The first forty consecutive male subjects in whom the maiu problem was a sexual dysfuuctiou or a psychiatric ilhless with accompauyiug sexual dysfuuctiou, were included in this study. Cases which proved secondary to au organic cause were excluded from the study. Results: The meau ages is 37.7110.5 years. All the samples were Muslims. Noue of the participants stated that they had homosexual experience or interest. 97.5 % (11=39) of all cases were regularly masturbating in adolescence. 46% (ii=1 8) stated that there is a sense of guilt because of masturbation 17.5 % (11~7) had stated that premarital sex or masturbation, would be a religious sin 67.5 % (11~27) stated that they had their first sexual intercourse in a brothel. 65% (11~26) learued the facts of life from a fiieud 25% (ir=lO) from books aud 10% (ii= 4) from movies. The ouset of the dysfuuctiou rauged betweeu 13 aud 57 years with au average of 3 1.33 years. The average duration betweeu