The effect of sodium metabisulphite on active avoidance performance in hypercholesterolemic rats

The purpose of this study was to investigate the effects of hypercholesterolemia and sulphite on active avoidance learning. Male Wistar rats were divided into eight groups as follows: Control (C), Sulphite (S), Vitamin E (E), Sulphite + Vitamin E (SE), Hypercholesterolemia (H), Hypercholesterolemia + Sulphite (HS), Hypercholesterolemia + Vitamin E (HE), and Hypercholesterolemia + Sulphite + Vitamin E (HSE). At the end of the experimental period, the serum cholesterol level (mean ± SD) was significantly higher in H group (111.5 ± 11.11 mg dL(-1) ) as compared to C group (63.5 ± 4.9 mg dL(-1) ). Levels of thiobarbituric acid reactive substances (TBARS) were increased in HS group as compared to C, H, and S groups. Vitamin E reduced TBARS levels in HSE group compared with HS group. Active avoidance results indicated that hypercholesterolemia was associated with learning impairment. Our data clearly revealed that the combination of hypercholesterolemia and sulphite results in exaggerated impairment of active avoidance. Vitamin E improved active avoidance in HSE group compared with HS group. Therefore, the synergistic effect of hypercholesterolemia and sulphite may be associated with a considerable health risk.     

The effect of sodium metabisulfite on visual evoked potentials in rats with hypercholesterolemia

This study aimed to investigate the effects of hypercholesterolemia on visual evoked potentials (VEPs) and sulfite additional effects. Rats were assigned as follows: control (C), sulfite (S), hypercholesterolemia (H), vitamin E (E), sulfite + vitamin E (SE), hypercholesterolemia + sulfite (HS), hypercholesterolemia + vitamin E (HE), and hypercholesterolemia + sulfite + vitamin E (HSE). Hypercholesterolemic diet led significant increase in plasma cholesterol levels of rats. Brain thiobarbituric acid reactive substances (TBARS) levels were significantly increased in S, E, SE, HE and HSE groups compared with C. TBARS levels were increased in HE and HSE groups as compared to HS group. Nitrite levels were decreased in S, SE, H, HS and HSE groups compared with C. Nitrite level was notably increased in the HE group compared with H group. Sulfite exposure prolonged N1 and P3 latencies of VEP in group S compared with C. Prolonged VEP latencies by sulfite were significantly decreased by vitamin E in SE group. Cholesterol rich diet increased VEP latencies in comparison with control latencies. Sulfite gave rise to an additional increase in P3 latency in HS group compared with H group. Vitamin E-treated animals had notably shortened latencies of VEP components in HE and HSE groups according to the H and HS groups, respectively.     

Effect of sulfite on red blood cell deformability ex vivo and in normal and sulfite oxidase-deficient rats in vivo

The effect of sulfite, a widely used food additive, on red blood cell deformability ex vivo and in vivo was investigated. Ex vivo experiments were conducted in human blood exposed to sulfite (5, 10 and 20 mM). In vivo experiments were carried out in sulfite oxidase-competent (SOXC) and sulfite oxidase-deficient (SOXD) rats. In the in vivo experiments, sulfite was administered in the form of sodium metabisulfite (Na₂S₂O₅, 25 mg/kg/day) via drinking water. Vitamin E dissolved in olive oil at a dose of 50 mg/kg was administered by gastric gavages. Red blood cell (RBC) deformability was determined at various fluid shear stresses using an ektacytometer. Ex vivo sulfite exposure to RBC did not affect RBC deformability. In the in vivo experiments, although RBC deformability was not affected by sulfite treatment in SOXD rats, it was found to be significantly increased in SOXC rats. Vitamin E treatment in combination with sulfite caused impairment in RBC deformability in both SOXC and SOXD rats. We suggest that sulfite needs to be oxidized in order to improve RBC deformability.     

Effects of phencyclidine on active avoidance and escape in rats

Rats trained to avoid electrical shock in a shuttle box were given phencyclidine (0.0, 1.0, 5.0, or 10.0 mg/kg) prior to testing for 5 consecutive days. There was a dose-dependent increase in both avoidance and escape failures although animals continued to cross the barrier during intertrial intervals, indicating that they were capable of making the appropriate response. Little evidence of tolerance was found during the 5-day testing period.     

Luteinizing-hormone-releasing hormone modifies retention of passive and active avoidance responses in rats

The influence of posttraining subcutaneous administration of luteinizing-hormone-releasing hormone (LHRH) was tested on the retention of either active or passive avoidance conditioning in male rats. Injection of LHRH (200/kg) immediately after the acquisition of an active avoidance response (two-way shuttle behavior) enhanced retention of the response, assessed 7 days later. When the neuropeptide was injected immediately after a passive avoidance conditioning training, the effects varied with the intensity of the footshock applied. LHRH enhanced retention of avoidance training with weak footshock (0.20 and 0.35 mA) but impaired retention of training with strong footshock (0.70 and 1.0 mA). The effects of LHRH seem to be unspecific since they are similar to those observed after treatment with several hormones. The results are discussed based on the interactions between peripherally injected hormones and endogenous substances released following footshock. A modulatory effect on the monoaminergic pathway involved in memory storage processes is postulated.     

阿托伐他汀对谷氨酸引起大鼠神经元损伤保护作用机制的研究

目的探讨阿托伐他汀对谷氨酸所致培养大鼠皮层神经元损伤保护作用的机制。方法 MTT法测定细胞存活率;Hoechst33258核染色观察细胞凋亡的形态学改变;Western blot检测活性的半胱氨酸天冬氨酸蛋白酶-3(caspase-3)和钙蛋白酶Ⅰ蛋白表达水平。结果谷氨酸(100μmol.L-1)可使神经元细胞存活率下降,细胞凋亡百分比明显增加,活性的caspase-3和钙蛋白酶Ⅰ蛋白表达增加。阿托伐他汀明显对抗谷氨酸诱导的神经元存活率下降及细胞凋亡百分比增加,同时明显抑制活性的caspase-3和钙蛋白酶Ⅰ蛋白表达增加。磷酯酰肌醇-3激酶(phos-phoinositide3-kinase,PI3K)/磷酸化蛋白激酶B(protein ki-nase B,Akt)通路特异性阻断剂LY294002(10μmol.L-1)能抑制阿托伐他汀对抗谷氨酸引起神经元细胞存活率下降,细胞凋亡百分比增加及活性caspase-3和钙蛋白酶Ⅰ蛋白表达增加的作用。结论阿托伐他汀能够明显对抗谷氨酸引起的皮层神经元损伤作用,这种作用可能与激活PI3K/Akt信号转导通路有关。     

Effects of second-generation histamine H1 receptor antagonists on the active avoidance response in rats

1. The aim of the present study was to establish a new schedule of active avoidance response in rats to estimate the central effects of second-generation histamine H1 receptor antagonists. 2. With the new schedule, a rat was placed into a dark room. A sliding door was opened after a delay of 5 s and, unless the animal moved into the lit room, an electric shock was delivered for 3 s. With the conventional schedule, the sliding door was opened immediately after the rat was placed into the dark room. 3. Ketotifen, at a dose of 50 mg/kg, showed no significant effect on the retrieval of active avoidance response with the conventional schedule. However, with the new schedule, the drug caused significant inhibition of retrieval of the response, even at a dose of 10 mg/kg. 4. Epinastine showed no significant effect on retrieval of the active avoidance response, even at a dose of 50 mg/kg with the new schedule. 5. Cetirizine, at a dose of 50 mg/kg, caused a significant effect, indicating that cetirizine, at this dose, markedly inhibits memory retrieval. 6. Both olopatadine and loratadine had potent effects; at doses of 20 and 50 mg/kg, respectively, these agents showed significant inhibitory effects on retrieval of the response. 7. In conclusion, we have developed a new schedule of active avoidance response that can be used to estimate the central effects of second-generation histamine H1 receptor antagonists.     

ZMS对老年大鼠脑内NGF和BDNF的影响

目的　研究自然衰老大鼠脑内两种神经营养素与学习记忆的关系 ,以及中药活性成分ZMS的作用。方法　用Y 迷宫测试动物的学习记忆功能 ,酶联免疫吸附分析法测定脑组织中BDNF和NGF的含量。结果　老年大鼠的学习和记忆成绩比青年大鼠差 (P <0 0 1) ,脑组织中BDNF的水平降低 ,NGF的变化无显著性。老年鼠喂服ZMS 2mon后 ,学习和记忆能力改善 ,正确次数 /反应总时间比值提高 (P <0 0 1) ,同时BDNF含量也高于老年组 (P <0 0 1)。但是ZMS对脑内NGF含量无影响。结论　ZMS能提高增龄引起的脑BDNF降低 ,从而对神经元起保护作用 ,这可能是ZMS改善老年大鼠学习记忆功能的重要机制之一     

Forebrain serotonin and avoidance learning: Behavioural and biochemical studies on the acute effect of p-chloroamphetamine on one-way active avoidance learning in the male rat

The acute effects of p-chloroamphetamine (PCA) on one-way active avoidance learning and on central monoamine concentrations were examined in the male rat. The 5-HT specificity of the acute behavioural effect of PCA was examined in several experiments. PCA (0.08–5 mg/kg IP) injected 30–60 min before testing produced a dose-related impairment of both avoidance acquisition and retention. Pretreatment with the selective serotonin (5-HT) uptake inhibitors fluoxetine and zimelidine, but not the noradrenaline (NA) uptake inhibitor desipramine, resulted in a blockade of the avoidance deficit. Degeneration of brain 5-HT neurons by a high neurotoxic dose of PCA (2 × 10 mg/kg IP) 7 days prior to the administration of PCA also blocked the avoidance deficit. There was also a complete blockade of the PCA-induced avoidance deficit by pretreatment with metergoline, a central 5-HT receptor blocking agent. A 2.5 mg/kg dose of PCA examined 60 min after injection produced regional changes in the 5-HT levels preferentially in the forebrain region with significant reductions in the cerebral cortex, hippocampus and striatum while marginal effects were observed in the hypothalamus, midbrain and spinal cord. PCA failed to reduce dopamine and noradrenaline concentrations in the time- and dose-range of the avoidance deficit. Thus, the avoidance learning impairment appears to be specifically related to the acute release of endogenous 5-HT from presynaptic nerve endings possibly in the forebrain resulting in stimulation of postsynaptic 5-HT receptors. These findings indicate that 5-HT neurons in the forebrain play a role in active avoidance learning possibly by an involvement in memorial and/or retrieval processes.     

Effect of celecoxib and L-NAME on global ischemia-reperfusion injury in the rat hippocampus

Abstract

Transient global ischemia continues to be an important clinical problem with limited treatment options. The present study aimed to investigate the possible protective effects of celecoxib [a selective cyclooxygenase (COX-2) inhibitor] and N-omega-nitro-L-arginine methyl ester (L-NAME) [a nonselective nitric oxide synthase (NOS) inhibitor] against global ischemia-reperfusion (IR) induced biochemical and histological alterations in the rat hippocampus. Global ischemia was induced by bilateral clamping of the common carotid arteries for 60 minutes. Hippocampal cysteinyl aspartate-specific protease-3 (caspase-3) activity, nitrite/nitrate contents (NO_X), as well as COX-2 immunoreactivity in the hippocampal Cornu Ammonis 1 (CA1) subregion were dramatically increased 24 hours after global ischemia. After 72-hour of reperfusion, ischemia induced a selective, extensive neuronal loss in the hippocampus CA1 subregion. Celecoxib (3 and 5?mg/kg, intraperitoneally; i.p.), administered 30 minutes before ischemia and at 6, 12, and 22 hours of 24-hour reperfusion, caused significant reductions in hippocampal caspase-3 activity as well as the number of COX-2 immunoreactive (COX-2 ir) neurons in the CA1 subregion. Further, celecoxib (3 or 5?mg/kg, i.p.), administered 30 minutes before ischemia and at 6, 12, 22, and 48 hours of 72-hour reperfusion, provided a notable histological protection of hippocampal CA1 neurons. Meanwhile, L-NAME (3?mg/kg, i.p.), administered twice (immediately after ischemia and 45 minutes after starting the reperfusion period), effectively reduced the elevated NO_X level, decreased hippocampal caspase-3 activity and COX-2 immumoreactivity, and ameliorated ischemia-induced damage in the hippocampal CA1 subregion. The present study indicates that celecoxib and L-NAME might be neuroprotective agents of potential benefit in the treatment of cerebral ischemia.     

The effect of α-amanitin on passive and active avoidance acquisition in mice

-Amanitin, a specific and potent inhibitor of form II DNA-dependent RNA polymerase, produced greater than 98% inhibition of the enzyme in mouse brain within 2 h of intracerebroventricular (icv.) injection. Mice were given one trial passive avoidance training and retested on the task 4 h later. Mice treated with -amanitin 2 h before training or immediately after training demonstrated a retention deficit when compared to non-injected or saline injected controls.Active avoidance was trained for 1 h using a Sidman schedule with a drumturning response. Performance during the last 15 min of training was compared to performance in the first 15 min of a retesting session, 4 h after training. -Amanitin, 2 h prior to training reduced the number of responses, per cent escapes and per cent avoidances in the retesting session. Post-training injection of -amanitin significantly reduced the number of responses and per cent avoidances.Rotarod and spontaneous motor activity were not affected by -amanitin. Whole body temperature was slightly and transiently reduced in icv. administration of -amanitin.     

Influence of certain H1-blockers on the step-through active avoidance response in rats

The inhibitory effects of some newly developed H₁-blockers on the step-through active avoidance response in rats were studied in comparison with those of classical H₁-blockers. Single administration of diphenhydramine, pyrilamine, promethazine and chlorpheniramine caused dose-related depressant effects on the active avoidance response. Ketotifen and azelastine caused less potent inhibition than the classical H₁-blockers, while the effects of astemizole and oxatomide were almost negligible in suppressing the response. Following chronic administration of pyrilamine and promethazine, the acquisition of active avoidance response was significantly retarded compared with the control group, where-as new H₁-blockers caused a somewhat but not significantly slower acquisition than the control group. Chronic administration of astemizole and oxatomide caused only transient suppression of the response. However, classical H₁-blockers such as pyrilamine and promethazine caused sustained inhibition for as long as drug administration was continued.     

Effect of naloxone and amphetamine on acquisition and memory consolidation of active avoidance responses in rats

Pretraining IP injection of naloxone (0.3 mg/kg) or amphetamine (2 mg/kg) enhanced performance during acquisition, but did not improve retention of active avoidance responses in rats. Naloxone (0.1 or 3 mg/kg) had no effect on acquisition or on retention. The combination of naloxone (0.3 mg/kg) plus amphetamine (2 mg/kg) did not produce the facilitation observed when each of the two drugs was administered alone. Pretreatment with the higher dose of naloxone (3 mg/kg) blocked the facilitative effect of amphetamine on acquisition. Post-training administration of naloxone (0.3 mg/kg) or amphetamine (2 mg/kg) improved retention. Naloxone (0.1 or 3 mg/kg) had no effect. When naloxone and amphetamine were combined, at respective doses of 0.3 mg/kg and 2 mg/kg, the improvement did not occur, i.e., the higher dose of naloxone prevented the facilitative effect of amphetamine. In addition, an ineffective dose of amphetamine (0.5 mg/kg), given either pre-or post-training together with the lower dose of naloxone (0.1 mg/kg), produced a significant enhancement of acquisition or consolidation, respectively. The results are consistent with the possibility that naloxone might exert its facilitative action on acquisition and memory consolidation through the release of catecholaminergic systems from inhibitory influences of opioids.     

The effect of nimesulide versus placebo on hemostasis in healthy volunteers

Objective: The primary objective was to evaluate the effect of 7 days treatment with nimesulide on bleeding time. Blood coagulation, von Willebrand factor and platelet aggregation ex vivo were investigated as a secondary objective. Method: A randomised, double-blind, placebo-controlled, parallel group, single centre study performed on 20 healthy male volunteers who received either placebo or nimesulide 100 mg twice daily for 7 days. Bleeding time, platelet count and platelet aggregation, thromboplastin time (prothrombin time), activated partial thromboplastin time, fibrinogen, Factor VIII:C, vWF:Ag, vWF:RCof and platelet-rich plasma aggregation following stimulation with adenosine 5′-diphosphate, collagen, arachidonic acid, ristocetin, thrombin and thrombin receptor-activating peptide were measured at baseline (day 0), and then 3 h after the first (day 1) and last (day 7) treatment. Results: The bleeding times for all subjects remained within the normal range throughout the study period, with no significant differences between the two treatment groups. There were no significant changes from baseline in platelet aggregation studies or in any of the other haemostasis tests, with no significant differences between the two groups. No clinically significant adverse events were reported or observed. Conclusions: Daily administration of 200 mg nimesulide for 7 days neither prolongs bleeding time nor modifies any of the other haemostasis variables measured. The lack of interactions with important haemostatic mechanisms suggests that nimesulide may also be used in patients with bleeding problems. This expectation has still to be confirmed by clinical experience. Received: 6 October 1997 / Accepted in revised form: 5 March 1998     

The effects of fenfluramine and fluoxetine on the acquisition of a conditioned avoidance response in rats

This study tested a behavior-suppressing punishment system and how its activity may be altered by agents known to interrupt or enhance serotonergic (5-HT) transmission. Holtzman male albino rats were tested for shuttle box avoidance acquisition and intertrial responding either 1 or 8 h following daily injections of fenfluramine (FEN) or fluoxetine (FXT). When the drug-test interval was 1 h, a time when both drugs are presumably potentiating 5-HT activity, avoidance acquisition and intertrial responding were impaired. When testing occurred 8 h after drug treatment, a time when 5-HT levels are unaltered by FXT and are maximally reduced by FEN, these drugs had no effect on avoidance acquisition, but FEN produced an increase in intertrial responses whereas FXT did not. These results support the proposal of an inhibitory 5-HT system. Furthermore, these data demonstrate that FEN is capable of exerting a biphasic action on intertrial responding and suggest that the time interval between drug administration and behavioural testing is a crucial variable when investigating FEN.     

The effect of para-chlorophenylalanine and scopolamine on passive avoidance in chicks

Four-day-old Vantress x Arbor Acre chicks were treated for key-peck passive avoidance (PA) learning following intraperitoneal injections of parachlorophenylalanine (PCPA) and/or scopolamine. In Experiment 1, chicks were pre-treated with either three or five injections of PCPA (150 mg/kg) or saline across th first three posthatch days and then tested for PA learning on the fourth posthatch day. In Experiment 2, chicks were first pre-treated with three injections of PCPA (150 mg/kg) or saline, and then injected with either scopolamine (0.5 mg/kg) or saline 20 min prior to PA testing on the fourth posthatch day. Major findings were: (a) Chicks pre-treated with PCPA did not significantly differ from saline control chicks in either the acquisition or maintenance of response suppression during PA testing; (b) chicks injected with scopolamine were significantly disrupted in PA learning as compared to saline control chicks; and (c) PCPA pre-treatment did not significantly affect the scopolamine-induced disruption of PA learning. These findings, therefore, suggest that cholinergic, but not serotonergic, mechanisms are involved in PA learning of the young chick.     

The modulatory effects of high affinity GABAB receptor antagonists in an active avoidance learning paradigm in rats

It has been reported that selective GABA_B receptor antagonists can enhance cognitive performance in a variety of learning paradigms. This prompted us to examine the effects of some more potent and newly synthesised GABA_B antagonists CGP 71982, CGP 62349 and CGP 55845A in an active avoidance test in rats. A two-way active avoidance test with negative reinforcement was performed for the first 5 of 12 days of antagonist administration. CGP 71982 and CGP 55845A at all doses applied (0.01–1.0 mg/kg) had an improving effect on learning, and memory retention on day 12; the rats made more avoidances in both sessions compared to controls. CGP 62349 was only active at the lowest dose tested (0.01 mg/kg). The present study confirms that GABA_B receptor antagonists can enhance cognitive performance but provides no insight into the mechanism of action of these novel antagonists. Received: 4 August 1997/Final version: 28 November 1997     

U0126对谷氨酸神经毒性损伤模型大鼠的脑保护作用

目的 探索U0126对脑组织谷氨酸神经毒性的保护作用及可能机制。方法 健康成年雄性SD大鼠皮层注射 N-甲基-D-天冬氨酸（NMDA）建立脑组织谷氨酸神经毒性模型。首先,采用不同浓度 NMDA（50、100、200mmol/L）及处理不同时间（3、6、12、24 h）筛选最佳的建模条件。根据选定的最佳条件,实验设对照组、MAPK/ERK1/2抑制剂U0126单独处理组（2 g/L）、NMDA组（200 mmol/L）、不同浓度（0.5、1、2 g/L）U0126联合NMDA处理组。各组处理24 h后处死动物,脑组织切片后行HE染色组织评价损伤;蛋白质印迹法检测损伤部位环氧合酶-2（COX-2）、诱导型一氧化氮合酶（iNOS）、Caspase-3（活化形式）及磷酸化ERK1/2（p-ERK1/2）表达水平,确定U0126在脑组织谷氨酸神经毒性损伤中的保护作用。结果 （1）NMDA以时间和浓度依赖的方式导致大鼠皮层兴奋毒性损伤,激活MAPK/ERK1/2信号通路,加重脑组织损伤,选取200 mmol/L NMDA处理24 h进行建模。（2）与对照组相比,NMDA组脑损伤部位COX-2、iNOS、Caspase-3（活化形式）、p-ERK1/2表达明显增加。U0126+NMDA处理组与NMDA组相比,COX-2、NOS、Caspase-3（活化形式）、p-ERK1/2表达水平随U0126浓度升高而降低,脑损伤的面积显著减小。结论 U0126对大鼠皮层谷氨酸神经毒性损伤具有保护作用,其机制可能与抑制ERK1/2激活及其下游的炎症、凋亡信号途径有关。     

黄芪注射液对缺氧缺糖/复氧复糖大鼠海马神经元caspase-3表达的作用

目的观察黄芪注射液对缺氧缺糖/复氧复糖大鼠海马神经元凋亡相关基因caspase-3表达的影响。方法取原代培养8 d的大鼠海马神经元,随机分为4组:正常对照组、缺氧缺糖/复氧复糖组、黄芪注射液溶剂对照组和黄芪注射液组。除正常对照组外均进行缺氧缺糖0.5 h,再复氧复糖。各组于复氧复糖后0、0.5、2、6、24、48、72 h和120 h采用免疫组织化学染色法和Western blot检测caspase-3蛋白的表达,采用原位杂交检测海马神经元caspase-3 mRNA的表达。结果免疫组化结果显示:与正常对照组相比,除0 h和0.5h之外,缺氧缺糖/复氧复糖组各时间点海马caspase-3阳性神经元数目占神经元总数的百分率均明显增多(P<0.05),于24 h达到高峰。黄芪注射液溶剂对照组以上指标的变化趋势与缺氧缺糖/复氧复糖组相一致。黄芪注射液组除0 h和0.5 h之外,各时间点以上指标均比缺氧缺糖/复氧复糖组减少(P<0.05)。Western blot检测结果显示:除0 h和0.5 h外,各时间点缺氧缺糖/复氧复糖组海马神经元caspase-3蛋白的平均灰度值均较正常对照组明显增加(P<0.05),24 h最高;与缺氧缺糖/复氧复糖组相比,黄芪注射液溶剂对照组各时间点caspase-3蛋白的平均灰度值无变化(P>0.05),而黄芪注射液组除0 h和0.5 h外,在各个时间点caspase-3蛋白的平均灰度值明显降低(P<0.05)。原位杂交检测结果显示:caspase-3 mRNA阳性神经元形态、数目占神经元总数的百分率的变化趋势与caspase-3蛋白的变化趋势完全一致。结论黄芪注射液可抑制缺氧缺糖/复氧复糖大鼠海马神经元凋亡相关基因caspase-3的表达,从而抑制缺氧缺糖/复氧复糖大鼠海马神经元的凋亡。     

Effects of dopamine antagonists in a two-way active avoidance procedure in rats: interactions with 8-OH-DPAT,ritanserin, and prazosin

Using a conditioned avoidance procedure in rats, the present study examined the ability of 8-OH-DPAT, ritanserin, and prazosin to alter the effects of the dopamine antagonists, raclopride and haloperidol, on avoidance- and on escape responding. The 5-HT_1A agonist 8-OH-DPAT (0.16 mg/kg) significantly enhanced the inhibitory effects of both raclopride and haloperidol on the conditioned avoidance response and produced a small enhancement of the effects of haloperidol on escape failures. The α₁-adrenoceptor antagonist prazosin (0.63 mg/kg) significantly enhanced the effects of raclopride on the conditioned avoidance response, but enhanced the effects of only a single dose of haloperidol; prazosin did not alter the effects of either dopamine antagonist on escape failures. The 5-HT₂ antagonist ritanserin (0.16 mg/kg) failed significantly to alter the effects of the dopamine antagonists examined here. These findings suggest that blockade of 5-HT₂ receptors may not enhance the antipsychotic efficacy of D₂-like antagonists. Further, they confirm previous findings with respect to interactions between 5-HT_1A agonists and neuroleptics, and support the hypothesis that combined 5-HT_1A agonist/D₂-like antagonist properties may be of clinical importance. Received: 19 April 1996/Final version: 1 July 1996