P.1.c Basic neuroscience – Neuropharmacology S241 Methods: In the first part, inactive doses of selective NAergic ligands were administered intra-peritoneally (i.p) 45 min before testing, followed by the administration of DOI i.p, 30min prior to testing. Depletion of 5-HT and lesion of NA systems were carried out using p-CPA and DSP-4 respectively before the administration of DOI alone and the co-administration of DOI and clonidine. In the second part, inactive doses of selective GABAergic lig- ands were administered i.p. 45min before testing, followed by the administration of DOI i.p, 30 min prior to testing. In the third part, the monoamine concentrations were determined using HPLC methods in order to determine the variation of monoamine concentrations in different structures of brain before and after an exposure of the FPT. Finally, the micro-injections of DOI in hippocampus and periaqueductal gray were realized. A two- way ANOVA was employed for interaction studies following by a Sidak’s test. A Student t test and a one-way ANOVA following by Dunnett’s test were employed for monoamine concentrations and for DOI injections in structures respectively. Results: Only the a2-adrenoceptor agonists (clonidine 0.06 mg/kg, guanabenz 0.125 and 0.5 mg/kg and guanfacine 0.06 and 0.125 mg/kg) had an inhibitory effect on the anxiolytic-like activity of DOI 1 mg/kg (p < 0.001 for all interactions). The NA lesion and 5-HT depletion did not alter the DOI effect and the inhibitory effect of a2-adrenoceptor agonists (p>0.05). The benzodiazepine agonists (diazepam 0.03, 0.125 mg/kg and alprazolam 0.03, 0.125 mg/kg) and a GABAA receptor agonist (muscimol 0.25 mg/kg) potentiated the anxiolytic-like activity of DOI 1 mg/kg in the FPT (p < 0.001 for all interactions). The activity of DOI was inhibited by the co-administration of GABAA receptor antagonists (bicuculline 1 mg/kg, p < 0.05 and picrotoxin 0.125 mg/kg, p < 0.05) and GABAB receptor agonist (baclofen 0.25 and 1 mg/kg, p < 0.001). The quantification of monoamines in different brain structures after a FPT demonstrated a decrease in 5-HT and 5-HIAA concentration in the hippocampus (p < 0.05 and p < 0.001 respectively). The micro-injection of DOI (5 mg) in the hippocampus significantly increased and in the periaqueductal gray significantly decreased the number of punished passages accepted by mice in the FPT (p < 0.001 and p < 0.01 respectively). Conclusions: The a2-adrenoceptors seem to act only as a regulator of anxiolytic-like effect of DOI. The DOI and the a2- adrenoceptors act on others neurons than NA and 5-HT neurons. The results demonstrated an important effect of GABA system and more particularly GABAA system in the mechanism of action of DOI in the FPT. The micro-injection of DOI suggested that the activity of DOI in the FPT might be due to an activation of 5-HT2 receptors present in the hippocampus. P.1.c.033 Comparison of risperidone, olanzapine and quetiapine in relation to body weight, serum blood glucose and prolactin levels H.R. Chaudhry 1 ° , S. Niaz 1 , N. Arshad 2 , F. Peracha 3 , A. Ayub 4 , K.A. Mufti 5 . 1 Fatima Jinnah Medical College, Psychiatry Department, Lahore, Pakistan; 2 Sir Ganga Ram Hospital, PMRC, Lahore, Pakistan; 3 Sir Ganga Ram Hospital, Psychiatry Department, Lahore, Pakistan; 4 Fountain House, Psychobiological Research Centre, Lahore, Pakistan; 5Horizon, Department of Biological Psychiatry, Peshawar, Pakistan Background: The atypical antipsychotics are extensively used based on their clinical (positive and negative symptoms) and lesser side effect (extrapyramidal) profiles. However, the unique pharmacodynamic profiles and accumulating evidences suggest that certain atypical antipsychotics i.e. olanzapine and risperidone have considerable side effects of their own, including weight gain, elevated glucose and serum prolactin levels. Objective: To compare the effects of atypical antipsychotics risperidone, olanzapine and quetiapine on body weight, blood glucose and serum prolactin levels. Design: Quasi experimental design. Place of study: Out patient department of Psychiatry, Sir Ganga Ram Hospital and Free Psychiatric Clinic at Ahbab Hospital, Qila Lachman Singh, Ravi Road, Lahore Pakistan. Material and Method: A total number of 120 patients, diagnosed according to DSM-IV-TR as having schizophrenia and were assessed and enrolled over the period of 12 weeks. Patients were randomly assigned in three groups: risperidone (n = 40), olanzapine (n = 40) and quetiapine (n = 40). The demographic variables: age, sex, marital status, education and family history of psychiatric disorder were recorded. Positive and Negative Symp- tom Scale (PANSS) was used to assess the severity of symptoms and treatment response. Patients were monitored on body weight, blood glucose and serum prolactin levels at baseline and 15, 30, 60 and 90 days of taking study drugs. Results: The results were analyzed by using descriptive statis- tics. The present study had 83 (69.2%) males and 37 (30.8%) females with mean age of 35.4±9.59 years, having 24.89±11.29 months mean duration of illness. Out of the total sample, 61 (50.8%) patients reported positive and 59 (49.2%) reported negative history of psychiatric illness in the family. One-way Analysis of Variance (ANOVA) showed significant difference (p < 0.05) between three groups regarding body weight at post assessment (F = 6.4, df = 2, p < 0.05). Olanzapine treated patients showed increase in body weight (72.3±8.8 kg) as compared to risperidone and quetiapine treated patients (70.6±9.5 kg) and (65.4±8.7kg) respectively. Regarding blood glucose, significant difference found in three groups (p < 0.05) at post assessment (F = 28.3, df = 2, p < 0.05). Olanzapine treated patients showed raised blood glucose level at post assessment (166.6±53.2 mg/dl) as compared to risperidone (118.0±19.1 mg/dl) and quetiap- ine (115.0±18.5 mg/dl) treated patients. Risperidone treated pa- tients showed raised serum prolactin level (49.37±24.5 ng/dl) as compared to olanzapine and quetiapine treated patients (14.90±6.0 ng/dl) and 13.59±6.6 ng/dl). While quetiapine treated patients did not show significant rise in blood glucose, body weight and serum prolactin level as compared to olanzapine and risperidone treated patients. Conclusion: It has been shown that certain atypical antipsy- chotics are associated with weight gain, raised blood glucose and serum prolactin levels making patients vulnerable to undesired side effects. Monitoring of baseline body weight, blood glucose and serum prolactin levels during treatment with atypical antipsy- chotics seem useful.