P.I Affective disorders and antidepressants S4-87 unpredictable stress,intra-cranial selfstimulation or shortterm social iso- lationthesetwo peptides exerteffectsresembling thoseof antidepressants (Van Reeet al, 1994).In the presentstudythe influence of subcutaneously administered MIF-I and TRH on the behavioural changes induced by melatonin administration in the nucleus accumbens were investigated and compared with that of fJE (10-16). Peptide solution (1.5-15 JLglkg) or saline was injected subcutaneously followed 1 hour later by an injection with melatonin (10 ng dissolved in saline containing 1% acetic acid and 2% ethanol) or vehicle bilaterally into the nucleus accumbens. The rats were placed 30 min after the last injection in a circular perspex test cage and locomotor activity and the duration of sniffing were assessed for 3 min. Melatonin induceda reduction in locomotor activity andan increase in sniffing duration. All three peptides dose-dependently antagonized the behavioural changes induced by intra-accumbens administration of melatonin. MIF-I, TRH and fJE (10-16) were found to be approximately equipotent in this respect. The behavioural activity of these peptides in this test resembles that of antidepressant drugs as was demonstrated in previous studies while it was also shown that the dopamine antagonists haloperidol and sulpiride do not antagonize these melatonin-induced behavioural effects. It is tempting to speculate that the blockade of the action of melatonin in the nucleus accumbens may be essential for the antidepressant effects. Further research into the effects of melatonin and its interaction with fJE (10-16), MIF-I and TRH on a behavioural and biochemical levelmay lead to a better understanding of the processes that are involved in the etiology of depression and to the development of a newclassof antidepressant drugs. References Durlach-Misteli, C. and Van Ree, lM. (1992) Dopamine and melatonin in the nucleus accumbens may be implicated in the modeof action of antidepressant drugs,Eur.J. Pharmacol. 217, 15-21. VanRee,J.M., Durlach-Misteli, C. and Niesink, R.J.M. (1994) Animal studies on neuropeptides and depression, in: Psychopharmacology of Depression, eds. S. Montgomery and T.H.Com (Oxford University Press. Oxford) p. 31. IP.1.074I Potentiation of antidepressants with lithium or carbamazepine A. Suwalska, J. Rybakowski. Department of Adult Psychiatry. University of Medical Sciences. ul. Szpitalna 27/33, 60-572 Poznan, Poland Addition of lithium to ineffective or partially effective antidepressant treatments exerts enhancing effects on serotonergic function. Efficacy of this strategy in TRD is well established. Several authors have recently suggested that the addition of carbamazepine (CBZ) to ongoing inef- fective antidepressant treatment may also be a useful strategy in this condition. The purposeof this study was to evaluate the efficacy of potentiation of antidepressants with lithium or carbamazepine (CBZ) in the treat- ment -resistant depression and to determine variables which distinguish responders and non-responders in both groups. Method: Thirty patients withtreatment-resistant depression (10bipolar, 20 unipolar) were randomly allocated to treatment with addition of either lithium or carbamazepine to ongoing treatment. Drug-resistance was defined as a failure to respond to two adequate antidepressive treatments. Patients included in the study had at baseline a score of at least 18 on 17-item Hamilton Depression Rating Scale (HDRS). Response was defined as a final HDRS score of < 7, and partial response as a 50% or more reduction in HDRS score between baseline and after four weeks of treatment. Plasmacortisol, triiodothyronine (T3). thyroxine (T4)andthy- roid stimulating hormone (TSH) concentrations were measured prior to and at the end of the courseof treatments. The activity of the erythrocyte membrane sodium- and potassium activated adenosine triphosphatase pump (Na, K-ATPase) was determined in 13 lithium treated patients and 8 CBZ patients. Results: The baseline mean HDRS scores, plasma hormones concen- trations, and ATPase activity were not significantly different in lithium or CBZgroup. Lithium addition was effective in 13 of 18 patients (72.2%), among whom 4 patients were partial responders, five subjects showed no re- sponse. In CBZgroup,7 patients of 12 werejudged responders (58.3%), (2-partial response), 5 were non-responders. Rapid improvement (within seven days) was observed in 6 lithium responders, and in 3 CBZ re- sponders (46.1% and 42.9%, respectively). There were no differences in improvement rates between the two groups (chi square = 0.625). Treatment with both lithium and CBZ was associated with significant decrease in plasmaT4 and increase in TSH concentration. Our findings suggest that potentiation of antidepressants with CBZ deserves further studyas a possible strategy for patients with TRD. I P.1.075! Mianserin therapy of depressive patients with coexisting cardiovascular diseases JolantaRajewska, Andrzej Rajewski. Department of Psychiatry K. Marcinkowski, University of Medical Sciences Szpitalna 27/33. 60-572 Poznan, Poland A great therapeutic problem is the treatment of patients with the major depression who havegot circulatory disorder. The conventional tricyclic antidepressants, effective in depression therapy, display however car- diotoxic side effects. Mianserin is the antidepressant which does not influence significantly the circulatory system. Its clinical antidepressant efficacy is comparable to the triciclic drugs. The purpose of this work is to estimate the possibility of using Mianserin (Lerivon-Organon) in the therapy of patients withmoderate-to- severe major depression and circulatory disorders. 20 patients (12 female and 8 male) aged from 37 to 68 were included to this study. Diagnosis was assessed according to DSMIV Criteria as majordepression in course of Major Depressive Disorder, Recurrent or Bipolar Affective Disorder. For evaluation of clinical state the Hamilton Depression Rating Scale (HAM-D) of 2l-item was used, mean values was 30 (ranging for 24-40). Mianserin (Lerivon-Organon) was used in doses 60-120 mg/day. Before starting the treatment the patients had the following cardiovascular dis- eases: Hypertonia arterialis -7 persons, Angina pectoris instabilis - 4, Statuspost infarctus cordis- 2, Myocardosis artherosclerotica - 5. Beside the antidepressive treatment the patients received cardiovascu- lar drugs. The period of active depression treatment was 6 to 18 weeks. Before starting the therapy every patient was examined somatically, had laboratory tests and ECG record. During the treatment the ECG was performed on the 3 rd , 7 th , 14 th , 21 st day of therapy and next with 2 weeks intervals. Systematic controls of blood pressure and heart-rate were made. Mianserin treatment in no way increased the circulatory symptoms stated clinically before. In the ECG records there were no traces of new abnormalities as well as increasing the existing disturbances. Subjective complaints of patients were observed as follows: daytime drowsiness, weakness and occasionally hypotension. In no caseit was required to stop the treatment because of these disturbances. Our results proved that Mianserin can be safety given to patients with major depression. It is clinically effective antidepressant and at the sametime well tolerated by patients with cardiovascular diseases before introduction of antidepressant treatment. I P.1.076I The NMDA receptor andthe olfactory bulbectomised rat model of depression A.M. Redmond, J.P. Kelly, B.E. Leonard. Department of Pharmacology, University College Galway, Ireland The N-methyl-D-aspartate (NMDA) subtype of glutamate receptor is one of several mediating excitatory amino acid synaptic transmission. Recent evidence suggests that this receptor subtype may be a site of antidepressant action. Radioligand binding studies indicate that NMDA receptor dynfunction mayoccurin depression. In frontal cortical samples fromsuicide victims, the specific binding of [3H]CGP-39653 (a competitive antagonist at the glutamate site) and the proportion of high affinity, glycine displaceable [3H]CGP-39653 binding sites was reduced in suicide victims compared to control subjects who died from natural causes (Nowak et al., 1995). Alterations in this receptor complex at the glycine site have been found to occur in the olfactory bulbectomised (DB) rat model of depression; such adaptations produced by DB are reversed by some but not all an- tidepressants (Redmond et al., in preparation). Following DB,the NMDA