Comparative in vitro activity of nine antistaphylococcal agents against 275 recent isolates of Gram-positive cocci

The aim of this study was to compare the in vitro activities of 9 antistaphylococcal agents including teicoplanin (TEI) against 275 non-repetitive clinical strains representing 15 species of staphylococci and 27 strains of Enterococcus (E.) faecalis, isolated from various specimens between 1991-1992 at a Canadian teaching hospital. The NCCLS agar dilution method was used (10(4) colonyforming units/spot). In terms of MIC(90), TEI and vancomycin (VAN) appeared to be the most potent antibiotics against all staphylococci tested (TEI: 2.0-4.0 mug/ml; VAN: 1.0-2.0 mug/ml; ciprofloxacin (CPF): 0.25-32 mug/ml; cefazolin (CEF): 8.0-256 mug/ml; methicillin (MET): 2.0->256 mug/ml; imipenem (IMP): 1.0-32 mug/ml; erythromycin (ERT): 16->256 mug/ml; ampicillin (AMP): 16-128 mug/ml; fusidic acid (FSA): 0.5-16 mug/ml). Multiple resistant strains, including MET-resistant Staphylococcus (Staph.) aureus and Staph. epidermidis, were susceptible to TEI and VAN with respective MICs of 2-4 mug/ml and 1-2 mug/ml regardless of specimen type. Moreover, TEI was highly active against E. faecalis (MIC(90) for TEI and VAN: 0.5 and 4.0 mug/ml, respectively).     

7-[(2S)-2-羟甲基-4-氨基-1-吡咯烷基]氟喹诺酮类化合物的合成及体外抗菌活性

用反式-L-羟脯氨酸经对甲苯磺酰氯保护、甲酯化、氧化、肟化、四氢铝锂还原、叔丁氧基羰基保护后脱除对甲苯磺酰保护基,与不同的氟喹诺酮中间体缩合,最后经脱除叔丁氧基羰基等反应得到目标物,结构经1HNMR和FAB-MS确证,并进行了体外抗菌活性试验.结果表明,除化合物13对供试的大部分菌株,特别是对链球菌的体外活性相当于或优于对照药加替沙星和环丙沙星外,其余3个目标物总体活性均低于对照品.     

利福霉素等6种抗菌药物对金葡球菌体外抗菌作用比较研究

目的 比较利福霉素、甲氧西林、氟氧头孢、美洛培南、奈替米星、万古霉素对mecA基因阳性和mecA基因阴性的金葡球菌的体外抗菌活性。方法 采用多重PCR方法检测金葡球菌的mecA基因携带情况,采用平皿二倍稀释法进行6种抗菌药物的最低抑菌浓度的测定。结果 6种抗菌药物对mecA 基因阴性的金葡球菌的MIC50和MIC90分别为甲氧西林（2、4mg/L), 利福霉素（0．125、0．25mg/L）,氟氧头孢（0．5、2mg/L）,美洛培南（0．25、0．25mg/L）,奈替米星（2、2mg/L）,万古霉素（2．2mg/L）。对mecA基因阳性的金葡球菌的MIC50和MIC90分别为甲氧西林（＞256、＞256mg/L),利福霉素（0．031、0．031mg/L）,氟氧头隐(32、64mg/L）,美洛培南（64、128mg/L）、奈替米星（32、64mg/L）,万古霉素（4、4mg/L）。结论 6种抗菌药物对mecA基因阴性的金葡球菌均有很强的体外抗菌活性,但对mecA基因阳性且对甲氧西林耐药的金葡球菌,氟氧头孢、美洛培南和奈替米星的体外抗菌活性差,万古霉素和利福霉素具有很强的体外抗菌活性,特别是利福霉素对于MRSS的抗菌活性明显强于MSSA。     

Antiplatelet and calcium inhibitory properties of eugenol and sodium eugenol acetate

• 1.1. Eugenol (3-methoxy-4-hydroxy-propenylbenzene) or sodium eugenol acetate (4-0-acetic acid sodium-3-methoxy-l-propenylbenzene) (0.25, 0.5, 1 mM) concentration-dependently inhibited arachidonic acid (AA)., collagen-, epinephrine- and ADP-induced platelet aggregation.
• 2.2. Eugenol or sodium eugenol acetate inhibited collagen-induced aggregation of washed rabbit platelets synergistically with creatine phosphatelcreatine phosphokinase (CP/CPK, 5 mM/10 U/ml) or p-bromophenacyl bromide (p-BPB, 10 μM), and they also potentiated the inhibitory action of imidazole (0.5 mM) on AA-induced aggregation.
• 3.3. Eugenol or sodium eugenol acetate (0.25, 0.5, 1 mM) concentration-dependently inhibited AA-induced thromboxane B₂ and prostaglandin E₂ formation.
• 4.4. The rise of intracellular Ca²⁺ caused by collagen, epinephrine, ADP, and AA were inhibited by eugenol or sodium eugenol acetate (1 mM).

     

In vitro antibacterial activity of ceftobiprole against clinical isolates from French teaching hospitals: proposition of zone diameter breakpoints

The aims of this study were to determine the in vitro activity profile of ceftobiprole, a pyrrolidinone cephalosporin, against a large number of bacterial pathogens and to propose zone diameter breakpoints for clinical categorisation according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) minimum inhibitory concentration (MIC) breakpoints. MICs of ceftobiprole were determined by broth microdilution against 1548 clinical isolates collected in eight French hospitals. Disk diffusion testing was performed using 30 μg disks according to the method of the Comité de l’Antibiogramme de la Société Française de Microbiologie (CA-SFM). The in vitro activity of ceftobiprole, expressed by MIC_50/90 (MICs for 50% and 90% of the organisms, respectively) (mg/L), was as follows: meticillin-susceptible Staphylococcus aureus, 0.25/0.5; meticillin-resistant S. aureus (MRSA), 1/2; meticillin-susceptible coagulase-negative staphylococci (CoNS), 0.12/0.5; meticillin-resistant CoNS, 1/2; penicillin-susceptible Streptococcus pneumoniae, ≤0.008/0.03; penicillin-resistant S. pneumoniae, 0.12/0.5; viridans group streptococci, 0.03/0.12; β-haemolytic streptococci, ≤0.008/0.016; Enterococcus faecalis, 0.25/1; Enterococcus faecium, 64/128; Enterobacteriaceae, 0.06/32; Pseudomonas aeruginosa, 4/16; Acinetobacter baumannii, 0.5/64; Haemophilus influenzae, 0.03/0.12; and Moraxella catarrhalis, 0.25/0.5. According to the regression curve, zone diameter breakpoints could be 28, 26, 24 and 22 mm for MICs of 0.5, 1, 2 and 4 mg/L respectively. In conclusion, this study confirms the potent in vitro activity of ceftobiprole against many Gram-positive bacteria, including MRSA but not E. faecium, whilst maintaining a Gram-negative spectrum similar to the advanced-generation cephalosporins such as cefepime. Thus ceftobiprole appears to be well suited for the empirical treatment of a variety of healthcare-associated infections.     

Safety signal withdrawal: a behavioural paradigm sensitive to both “anxiolytic” and “anxiogenic” drugs under identical experimental conditions

A new method involving the blockade of operant behaviour induced by the withdrawal of a conditioned signal for safety without presentation of a punishment signal has been developed for studying drugs with anxiolytic or anxiogenic properties. For this purpose, rats were trained under two alternating components of a multiple schedule of reinforcement FR8 (food)/FR1 (food) + RR 50% (shocks randomly delivered with 50±15% of the presses). The nonpunished and punished periods were signalled by one cue light above the right lever (safety signal) or the left lever (punishment signal), respectively. On the test session (safety signal withdrawal), the safety signal was turned off at the end of the first nonpunished period, but the punishment signal was not presented (every press was food rewarded and no shocks were delivered). During this period (4 min), rats exhibited a strong blockade of responding that lessened over time. This suppression seemed not to be caused by intervening events such as novelty, temporal conditioning, schedule of food delivery or ambiguity of the signal presented. The behavioural blockade induced by withdrawal of the safety signal was reduced by benzodiazepines: diazepam (0.5–4 mg/kg), chlordiazepoxide (4–8 mg/kg), nitrazepam (0.25–2 mg/kg), alprazolam (0.25–1 mg/kg), and partial agonists at benzodiazepine receptors: bretazenil (0.125–8 mg/kg) and ZK 91296 (32–64 mg/kg). Various 5-HT-related drugs also lessened the behavioural blockade: pCPA (3×150 mg/kg) and the 5-HT1A receptor agonists, buspirone (0.25–2 mg/kg), gepirone (0.25–1 mg/kg) but not 8-OH-DPAT. Compounds that may cause anxiety in humans further enhanced the blockade of lever pressing induced by the safety signal withdrawal at doses that did not modify baseline responding:d-amphetamine (0.125–0.5 mg/kg), caffeine (16 mg/kg) and picrotoxin (1 mg/kg). FG 7142 (8 mg/kg) and CGS 8216 (2–8 mg/kg) decreased responding during both components of the session. Therefore, the present paradigm seems sensitive to both anxiolytic and anxiogenic effects of drugs under identical procedural conditions.     

In vitro evaluation of G1: a novel antimicrobial compound

G1 (1-[5-bromofur-2-il]-2-bromo-2-nitroethene) is a novel antimicrobial compound developed in Cuba with reported broadspectrum activity against Gram-positive and -negative bacteria, yeasts and fungi. A compound of this nature may have considerable therapeutic potential. We tested the in vitro activity of this novel compound against 3595 organisms using microbroth dilution. The following are MIC50, MIC90 and range respectively for some of the microorganisms tested: E. coli 16, 16, 4 32; Klebsiella sp. 16, 16, 8 32; Citrobacter sp. 16, 16, 8 16; Enterobacter sp. 16, 16, 8-16; Proteus sp. 16, 16, 8-16; Coagulase-negative staphylococci 16, 32, 4-32; Enterococcus sp. 16, 32, 2-32; Staphylococcus aureus 8, 16, 4-16; Streptococcus agalactiae 4, 8, 4 8; Streptococcus pyogenes 4, 8, 0.25-16; Candida albicans 2, 2, 1-4; Candida tropicalis 4, 4, 2-4; Candida sp. 2,4, 1-4. MIC values appear lower for Gram-positive microorganisms and yeasts. G1 appears to be a novel antimicrobial agent with broad spectrum activity against bacterial and fungal pathogens. Defining the activity of this compound against multi-resistant bacteria is a priority.     

Changed preference for sweet taste in adulthood induced by perinatal exposure to bisphenol A-A probable link to overweight and obesity

Background

The preference of obesity has risen dramatically worldwide over the past decades. Some latest reports showed significant increase of obesity in men compared to women. Implication of environmental endocrine disruptors has been focused more and more. Numerous studies in vitro and vivo implied metabolic actions of bisphenol A (BPA), however much less consideration is given to the possibility of BPA exposure-induced change in gender-specific behaviors which result in obesity and overweight.

Objectives

To examine whether perinatal exposure to BPA at relative dose to environmental levels can influence sweet preference of male and female rats and consequently lead to alteration in bodyweight.

Methods

Rats perinatally exposed to BPA at doses of 0.01, 0.1 and 1.0 mg/L were tested sweet preference for 0.25%, 0.5% saccharin and 15% sucrose by two-bottle choice (water vs. saccharin/sucrose). The food intake, liquid consumption and bodyweight of each rat were monitored daily. At the end of the test, the fat percentage and tail blood pressure were measured.

Results

Significant sex difference of preference for 0.25% and 0.5% saccharin was shown in control and all BPA-treated groups (p < 0.001, female vs. male). 0.1 and 1.0 mg/L BPA treatment induced the increase of preference for 0.25% saccharin solution in males, but not in females. 0.1 mg/L BPA treatment increased sucrose preference in males at postnatal day (PND) 70 and 140 (p < 0.05 and p < 0.001, compared to control respectively) but decreased sucrose preference in females at PND 140 (p < 0.05, compared to control). The males treated by BPA showed overweight (p < 0.001), high fat percentage (p < 0.001) and tail blood pressure (p < 0.05) than control at PND 140.

Conclusion

Perinatal exposure to a low dose of BPA could increase sweet preference of male rats. Calorie intake may be programmed during early life, leading to changes of body weight depending on the gender. Although further researches concerning the mechanism are required, the results of the present study are particularly important with regards to the more significant increasing prevalence of obesity in men and the environmental endocrine disruptors.     

Bromocriptine induces climbing behaviour: possible D-1 or D-2 dopamine receptor involvement

The ability of bromocriptine (BRC), a dopamine D-2 receptor agonist, to induce climbing behaviour was studied in mice. BRC (2–32 mg/kg IP) evoked climbing behaviour. The maximum effect was obtained with 8 mg/kg, while higher doses of BRC (16 and 32 mg/kg) were less effective. Climbing began about 2 h after injection and was most marked 5 h after bromocriptine administration. Pretreatment of animals with the dopamine antagonist pimozide (0.5 mg/kg IP) decreased BRC-induced climbing. Sulpiride (0.25–1.25 mg/kg IP), a potent D-2 antagonist and/or SCH 23390 (0.025 and 0.05 mg/kg SC), a D-1 receptor antagonist, also decreased the response. Furthermore, the climbing behaviour induced by BRC was abolished by pretreatment with reserpine plus alpha-methyl-p-tyrosine (AMPT). Concomitant administration of apomorphine (APO) and BRC potentiated the effect of APO on climbing. Concomitant injection of BRC and SKF 38393 (SKF, D-1 agonist) reduced the effect of SKF on climbing, while administration of BRC 4 h before SKF potentiated the effect of both drugs. It is suggested that BRC induces climbing through D-1 and/or D-2 dopamine receptors.     

手法小切口白内障手术治疗糖尿病性白内障的疗效分析

目的分析手法小切口白内障摘除联合人工晶状体植入术治疗糖尿病性白内障的疗效。方法对68例(96眼)糖尿病合并白内障的患者行小切口白内障摘除及人工晶状体植入术的临床资料进行回顾性分析。统计术后1、30d的视力,术后视力与糖尿病病程的关系以及术后并发症。结果术后第1天裸眼视力>0.5者69眼(71.88%),0.3～0.5者18眼(18.75%),0.1～0.25者6眼(6.25%),<0.1者3眼(3.13%);术后第30天裸眼视力>0.5者74眼(77.08),0.3～0.5者16眼(16.67%),0.1～0.25者4眼(4.17%),<0.1者2眼(2.08%)。术后并发症主要有角膜水肿、前房纤维素性渗出、虹膜粘连、继发青光眼。结论手法小切口白内障摘除联合人工晶状体植入术治疗糖尿病性白内障是安全有效的,术后视力的恢复与糖尿病病程及糖尿病视网膜病变有关。     

Despite various drugs,cats continue to kill mice

Amphetamines (d- at 0.5–4 mg/kg; 1- at 2–4 mg/kg) inhibited spontaneous mouse killing by some, but not all cats. Various other drugs (drugs and maximum tested doses were: imipramine, 64 mg/kg; amitriptyline, 32 mg/kg; tranylcypromine, 2 mg/kg; tripelennamine, 4 mg/kg; scopolamine, 1 mg/kg; methyl scopolamine, 1 mg/kg; chlordiazepoxide 16 mg/kg; diazepam 4 mg/kg; meprobamate, 80 mg/kg; pentobarbital, 16 mg/kg; chlorpromazine, 8 mg/kg; and haloperidol, 0.5 mg/kg) did not reliably inhibit such killing. In contrast with rats, mouse killing by cats was not consistently blocked by antidepressants or amphetamines. When individual cats were inhibited, their reduction of killing seemed related to anorexia rather than to affective arousal.     

山楂果胶寡糖联用氟喹诺酮类药物对葡萄球菌防耐药浓度的影响分析

目的 探讨山楂果胶寡糖与氟喹诺酮联合用药对金黄色葡萄球菌防耐药浓度的影响,为临床合理使用现有抗生素、防治细菌耐药产生提供理论依据.方法 采用标准琼脂二倍稀释法测定左氧氟沙星、环丙沙星对30株临床分离的金黄色葡萄球菌和金黄色葡萄球菌质控菌株ATCC25923的最低抑菌浓度(MIC),采用标准琼脂平板稀释法测定2种FQ药物对临床分离金黄色葡萄球菌的防突变浓度,计算单药和联合山楂果胶寡糖用药后该药的MPC50、MPC90.结果 左氧氟沙星单药对30株金黄色葡萄球菌的MPC范围在2～64mg/L,MPC90为32mg/L;联合山楂果胶寡糖后MPC范围为0.5～16 mg/L,MPC90降至8 mg/L.环丙沙星单药对30株金黄色葡萄球菌的MPC范围1～32mg/L,MPC90为16mg/L;联合山楂果胶寡糖后MPC范围0.25～8mg/L,MPC90降至4 mg/L,两组各项指标比较差异有显著性(P<0.05).结论 联合山楂果胶寡糖用药能降低环丙沙星、左氧氟沙星MPC,减少细菌耐药突变体的选择性富集扩增,防止抗菌药物耐药的产生.     

山楂果胶寡糖联用氟喹诺酮类药物对葡萄球菌防耐药浓度的影响分析

目的探讨山楂果胶寡糖与氟喹诺酮联合用药对金黄色葡萄球菌防耐药浓度的影响,为临床合理使用现有抗生素、防治细菌耐药产生提供理论依据。方法采用标准琼脂二倍稀释法测定左氧氟沙星、环丙沙星对30株临床分离的金黄色葡萄球菌和金黄色葡萄球菌质控菌株ATCC25923的最低抑菌浓度（MIC）,采用标准琼脂平板稀释法测定2种FQ药物对临床分离金黄色葡萄球菌的防突变浓度,计算单药和联合山楂果胶寡糖用药后该药的MPC50、MPC90。结果左氧氟沙星单药对30株金黄色葡萄球菌的MPC范同在2～64mg／L,MPC90为32mg／L;联合山楂果胶寡糖后MPC范围为0．5～16mg／L,MPC90降至8mg／L。环丙沙星单药对30株金黄色葡萄球菌的MPC范围1～32mg／L,MPC90为16mg／L;联合山楂果胶寡糖后MPC范围0．25～8mg／L,MPC90降至4mg／L,两组各项指标比较差异有显著性伊〈0．05）。结论联合山楂果胶寡糖用药能降低环丙沙星、左氧氟沙星MPC,减少细菌耐药突变体的选择性富集扩增,防止抗菌药物耐药的产生。     

山楂果胶寡糖联用氟喹诺酮类药物对葡萄球菌防耐药浓度的影响分析

目的 探讨山楂果胶寡糖与氟喹诺酮联合用药对金黄色葡萄球菌防耐药浓度的影响,为临床合理使用现有抗生素、防治细菌耐药产生提供理论依据.方法 采用标准琼脂二倍稀释法测定左氧氟沙星、环丙沙星对30株临床分离的金黄色葡萄球菌和金黄色葡萄球菌质控菌株ATCC25923的最低抑菌浓度(MIC),采用标准琼脂平板稀释法测定2种FQ药物对临床分离金黄色葡萄球菌的防突变浓度,计算单药和联合山楂果胶寡糖用药后该药的MPC50、MPC90.结果 左氧氟沙星单药对30株金黄色葡萄球菌的MPC范围在2～64mg/L,MPC90为32mg/L;联合山楂果胶寡糖后MPC范围为0.5～16 mg/L,MPC90降至8 mg/L.环丙沙星单药对30株金黄色葡萄球菌的MPC范围1～32mg/L,MPC90为16mg/L;联合山楂果胶寡糖后MPC范围0.25～8mg/L,MPC90降至4 mg/L,两组各项指标比较差异有显著性(P<0.05).结论 联合山楂果胶寡糖用药能降低环丙沙星、左氧氟沙星MPC,减少细菌耐药突变体的选择性富集扩增,防止抗菌药物耐药的产生.     

Surveillance of antimicrobial resistance of Streptococcus pneumoniae isolates from the Kinki Region of Japan during 2003/2004. The Surveillance Program of Bacterial Resistance in the Kinki Region of Japan; SBRK

Three hundred seventy five isolates of Streptococcus pneumoniae were collected from 14 medical institutions in the Kinki region of Japan between November 2003 and February 2004. We determined the minimum inhibitory concentration (MIC) of penicillin G (PCG) and 25 of other antimicrobial agents against these isolates according to the National Committee for Clinical Laboratory Standards (NCCLS). Overall, 71.5% of all isolates were resistant to PCG (intermediate and resistant categories were 51.7% and 19.8%, respectively). For the carbapenems and penem, the rank order of activity was PAPM (MIC90, 0.12 microg/ml) > IPM (0.25 microg/ml) > MEPM (0.5 microg/ml) = FRPM (0.5 microg/ml). For the cephems, the overall rank order of activity was CPR (MIC90, 0.5 microg/ml) = CDTR (0.5 microg/ml) > CTRX (1 microg/ml) = CTX (1 microg/ml) = CZOP (1 microg/ml) = CFPN (1 microg/ml). Rank order activity for six of fluoroquinolones was TFLX = MFLX (MIC90, 0.25 microg/ml) > GFLX (0.5 microg/ ml) = SPFX (0.5 microg/ml) > LVFX (1 microg/ml) > PZFX (4 microg/ml). The rate of resistance to fluoroquinolones per the NCCLS criteria were very low, ranging from 0.7% to 2.6%. Rate of resistance to other antimicrobiotics were CAM, 77.0%; CLDM, 41.7%; TEL, 0%; VCM, 0%; ST, 32.7%, and CP, 21.4%.     

The effects of dopamine receptor agents on naloxone-induced jumping behaviour in morphine-dependent mice

In the present study, the effects of dopamine receptor agonists and antagonists on naloxone-induced jumping in morphine-dependent mice were examined. Mice were rendered dependent as described in the methods section. Naloxone was injected to elicit jumping (as withdrawal sign). The first group received dopamine receptor drugs before naloxone injection to test the effects of the drugs on the expression of jumping. Administration of the dopamine D1/D2 receptor agonist, apomorphine (0.25, 0.5 and 1 mg/kg), decreased jumping, but not diarrhoea, induced by naloxone. The effect of apomorphine on jumping was reduced by the dopamine D2 receptor antagonist, sulpiride. The dopamine D2 receptor agonist, quinpirole (0.1, 0.3 and 0.5 mg/kg), increased jumping, while it decreased diarrhoea in mice. Different doses of sulpiride did not alter jumping, but one dose of the drug (12.5 mg/kg) decreased jumping. Neither the dopamine D1 receptor agonist, SKF38393 (1-phenyl-7,8-dihydroxy-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride; 8 and 16 mg/kg), nor the dopamine D1 receptor antagonist, SCH23390 (R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-benzazepine-7-ol maleate; 5, 10 and 25 mg/kg), altered jumping, but they decreased diarrhoea. The second group of animals received the drugs during the development of dependence. Administration of quinpirole (0.1, 0.3 and 0.5 mg/kg), but not bromocriptine (4, 8 and 16 mg/kg), apomorphine (0.25, 0.5, 1 and 2 mg/kg) or sulpiride (12.5, 25 and 50 mg/kg) decreased naloxone-induced jumping and diarrhoea. A dose of SKF38393 (8 mg/kg) decreased jumping, while both SKF38393 (4 and 16 mg/kg) and SCH23390 (5 and 10 microg/kg) increased diarrhoea. It is concluded that activation of both dopamine D1 and D2 receptors may suppress naloxone-induced jumping in morphine-dependent mice, and that stimulation of dopamine D1 receptors during development of morphine dependence may increase diarrhoea through peripheral mechanism.     

Dopaminergic system in CA1 modulates MK-801 induced anxiolytic-like responses

Rationale

Today, there is relatively no debate on the notion that NMDA receptor antagonist agents in the hippocampus induce anxiolytic-like effects through distinct mechanisms. There is also a bulk of studies showing the involvement of the dopaminergic system in NMDA induced behaviors. Thus, on the basis of the involvement of dopaminergic system in anxiety-related behaviors, the present study aimed to investigate the involvement of the dorsal hippocampal (CA1) dopaminergic system in anxiolytic-like responses induced by MK801 (NMDA receptor antagonist) in male Wistar rats.

Methods

We used the elevated plus maze to test anxiety. This apparatus has widely been employed to test parameters of anxiety-related behaviors including the open arm time percentage (%OAT), open arm entries percentage (%OAE), locomotor activity, grooming (the rat rubs its face), rearing (the rat maintains an erect posture) and defecation (the number of boli defection).

Results

The data showed that, intra-CA1 injection of MK801 (2 μg/rat) increases %OAT and %OAE but not other exploratory behaviors, indicating an anxiolytic-like effect. Moreover, sole intra-CA1 injection of SCH23390, dopamine D1 receptor antagonist, (0.25, 0.5 and 1 μg/rat) and sulpiride, dopamine D2 receptor antagonist, (0.25, 0.5 and 0.75 μg/rat) did not alter anxiety-like behaviors. Co-administration of subthreshold doses of SCH23390 (0.5 μg/rat) and MK801 (0.5 g/rat), induced anxiolytic-like behaviors. Furthermore, intra-CA1 administration of different doses of sulpiride (0.12, 0.5 and 0.75 μg/rat), 5 min before the injection of an effective dose of MK801 (2 μg/rat), decreased %OAT and %OAE, however did not alter other exploratory behaviors induced by MK801.

Conclusion

Our results suggested a modulatory effect of the CA1 dopaminergic system on the anxiolytic-like effects induced by MK801.     

Psychopharmacological profile of the selective serotonin reuptake inhibitor, paroxetine: implication of noradrenergic and serotonergic mechanisms

The present study was designed to evaluate the psychopharmacological profile of the selective serotonin reuptake inhibitor paroxetine, and thus assess potential noradrenergic and/or serotonergic activity. Paroxetine dose-dependently increased mobility time in the mouse forced swimming test (8, 16, 32 and 64 mg/kg, i.p.) and reduced spontaneous locomotor activity when administered at a high dose (64 mg/kg, i.p.). Prior administration of 8-hydroxy-2-(di-n-propylamino)tetralin (1 mg/kg, i.p.), (+/-) pindolol (32 mg/kg, i.p.) or 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridyl)-1H-indole (RU 24969) (1 mg/kg, i.p.) potentiated the antidepressant-like effects of subactive doses of paroxetine (1, 2 and 4 mg/kg, i.p.) in the mouse forced swimming test. These effects were antagonized by prior administration of 1-(2-methoxyphenyl)-4-[-(2-phthalimido)butyl]piperazine) (0.5 mg/kg, i.p.). Complementary studies suggested that RU24969-induced anti-immobility effects were a result of an increase in locomotor activity; other interactions were without increase/decrease in locomotor activity. Acute administration of paroxetine (8, 16, and 32 mg/kg, i.p.) antagonized the hypothermia induced by the D2/D1 receptor agonist, apomorphine (16 mg/kg, s.c.), while repeated treatment with paroxetine (32 mg/kg) attenuated clonidine-induced (0.5 mg/kg, i.p.) hypothermia. Pre-treatment with the serotonergic neurotoxin, para-chlorophenylalanine attenuated the anti-immobility effects of low doses of paroxetine (8 and 16 mg/kg, i.p.) in the forced swimming test, whereas a higher dose of paroxetine remained active (32 mg/kg, i.p.). The results of the present study indicated that paroxetine displayed both noradrenergic-like and serotonergic-like activity in the pre-clinical psychopharmacological tests employed.     

Low-frequency hearing loss following perinatal exposure to 3,3',4,4',5-pentachlorobiphenyl (PCB 126) in rats.

Previous research has demonstrated the sensitivity of the developing rat to the ototoxic effects of exposure to Aroclor 1254. In this study we assessed the effects of developmental exposure to an individual PCB congener (3,3',4,4',5-pentachlorobiphenyl; PCB 126) on auditory function. Nulliparous Long Evans rats received either 0, 0.25, or 1.0 microg/kg/day (5 days/week) for 35 days prior to breeding and throughout gestation and lactation. Auditory thresholds for 0.5-, 1-, 4-, 8-, 16-, 32-, and 40-kHz tones were assessed in offspring on postnatal days (PND) 76-90. Perinatal maternal PCB 126 exposure caused low-frequency hearing deficits. Elevated auditory thresholds occurred in the 1.0 microg/kg/day treated group for 0.5- and 1-kHz tones, whereas thresholds were not significantly affected at any higher frequencies. These results are important in that the data implicate, at least partially, the coplanar PCBs in the developmental ototoxicity induced by Aroclor 1254.