曲尼司特对豚鼠肺组织β肾上腺素受体向下调节的影响

用放射配体结合分析法分别测定了正常组、特布他林组、特布他林十曲尼司特组豚鼠的肺组织β受体最大结合力和解离常数,结果显示:给特布他林后豚鼠肺组织β受体发生明显的向下调节.曲尼司特可预防此向下调节的发生.     

Desensitization by terbutaline of beta-adrenoceptors in the guinea-pig soleus muscle: biochemical alterations associated with functional changes.

1 The effects of adrenaline and terbutaline on cyclic adenosine 3',5'-monophosphate (cyclic AMP) content, 22Na-efflux, 42K-influx and subtetanic contractions have been assessed in soleus muscles isolated from guniea-pigs which had been maintained on food with or without terbutaline for 5 days. 2 Terbutaline and adrenaline increased cyclic AMP content and suppressed subtetanic contractions, and regression analysis indicates a statistically significant correlation between these two effects (P less than 0.01). 3 In muscles obtained from terbutaline-treated animals, the effects of terbutaline and adrenaline on cyclic AMP content, active Na-K-transport and subtetanic contractions were all considerably suppressed, but insulin stimulated 22Na-efflux and affected subtetanic contractions to the same extent as in the muscles obtained from the control group. 4 The results suggest that terbutaline treatment leads to a reduction in the number of beta 2-adrenoceptors in skeletal muscle or an impairment of their function. 5 The results provide further support for the idea that the effect of adrenaline or insulin on skeletal muscle contractions is the outcome of stimulation of active Na-K-transport.     

In vivo induced desensitization of beta-adrenoceptors in rat lung. Effect of nitrendipine

The effect of nitrendipine on desensitization of beta-adrenoceptors induced by isoprenaline was investigated using rat lungs. Rats were treated with saline, isoprenaline, nitrendipine, or nitrendipine + isoprenaline. After 7 days of treatment, tracheas were isolated and the dissociation constant (Kb) for the propranolol-beta-receptor complex was determined. Lung parenchymal tissue was used to study the binding characteristics of beta-adrenoceptors. The Kb value for the propranolol-beta-receptor complex was found to be up to 6.4-fold higher in trachea isolated from isoprenaline-treated rats (32 +/- 5.4 nM) than from control rats (4.9 +/- 1.2 nM); the Kb value for trachea from isoprenaline + nitrendipine-treated rats was 7.0 +/- 1.2 nM. A 31% reduction in the number of beta-adrenoceptors as compared to those of the control group was observed in the isoprenaline-treated group while the number of the beta-adrenoceptors in the isoprenaline + nitrendipine-treated group was significantly increased as compared to that of the isoprenaline-treated group.     

Regulation of beta-adrenoceptors in the guinea pig left ventricle and skeletal muscle following chronic agonist treatment

Pretreatment of guinea pigs with adrenaline, isoprenaline or terbutaline for 7 days significantly reduced the Bmax for the radioligand [125I]cyanopindolol (ICYP) in the gastrocnemius muscle (beta 2-adrenoceptors). Pretreatment of guinea pigs with terbutaline reduced the responsiveness of gastrocnemius muscle slices adenylate cyclase to isoprenaline (10(-4) M). In the left ventricle (predominantly beta 1-adrenoceptors) pretreatment of guinea pigs with isoprenaline or adrenaline for 7 days did not alter the Bmax for ICYP. The responsiveness of adenylate cyclase to isoprenaline (10(-4) M) in left ventricle slices was significantly reduced following isoprenaline pretreatment of the guinea pigs. Thus desensitisation of beta-adrenoceptors in left ventricle and skeletal muscle developed following chronic agonist pretreatment. Reduction of beta 2-adrenoceptors in the skeletal muscle could be responsible for the desensitisation of adenylate cyclase. In the left ventricle the receptors were resistant to agonist induced down-regulation. It is proposed that other mechanisms which are tissue- and species-specific independent of the receptor subtype can be responsible for agonist-induced desensitisation in the left ventricle of the guinea pig in vivo.     

Effects of the phthalazinone azelastine on epidermal metabolism after mechanical skin irritation.

In female NMRI mice, the phthalazinone azelastine was administered orally once daily over 7 days. The drug influenced the epidermal thymidine triphosphate and amino acid incorporation rates at doses between 1 and 5 mg/kg. In control mice, an epidermal hyperproliferation induced by abrasion of superficial epidermal layers was characterized by enhanced prostaglandin and leukotriene concentrations in epidermal homogenate, an increase in thymidine triphosphate and amino acid incorporation and an increase in epidermal thickness. In mice treated with 1 mg/kg azelastine HCl, this epidermal reaction was changed. Compared to controls, the increase in leukotriene concentration was diminished, and that of prostaglandins was enhanced. The incorporation of thymidine triphosphate and of amino acids as well as the epidermal thickness and the ratio cell count/epidermal thickness were increased in irritated skin of azelastine-treated mice. In conclusion, azelastine influences the epidermal metabolism in irritated and unirritated skin. Therefore, a beneficial role of this phthalazinone in the treatment of psoriasis and related skin disorders seems to be possible.     

Comparison of the efficacy and tolerability of topically administered azelastine,sodium cromoglycate and placebo in the treatment of seasonal allergic conjunctivitis and rhino-conjunctivitis

Objective and setting: Azelastine (AZE) in a novel, eye drop, formulation, was compared with topically applied sodium cromoglycate (SCG) and placebo (PLA) in the treatment of seasonal allergic conjunctivitis or rhino-conjunctivitis in a multicentre, parallel group study. Research design: 144 subjects ranging in age from 16 to 65 years participated. All had at least a 2-year history of seasonal allergic conjunctivitis and were symptomatic at the time of inclusion. Medications were administered topically either twice daily (AZE/PLA) or four times daily (SCG) over a 2-week treatment period. Method and outcome measures: Azelastine and placebo were compared double-blind; the comparison versus SCG was carried out in an open manner. Itching, redness, flow of tears, eyelid swelling, foreign-body sensation, photophobia, soreness and discharge were scored on a 4-point severity scale. RESULTS: Results for the decrease of main conjunctivitis symptoms (itching, tearing and conjunctival redness) showed a marked effect for both active treatments on day 3 with a sustained improvement on days 7 and 14. A clear response to treatment (an improvement of sum scores for day 3 of >/=3 points compared to baseline) occurred in 85.4% of azelastine-treated patients, 83.0% of sodium cromoglycate patients and 56.3% of placebo patients. Response rates for both active treatments were statistically superior to those for placebo (azelastine p = 0.005; sodium cromoglycate p = 0.007). Global assessment of efficacy was at least 'satisfactory' for 90.0% of azelastine patients, 81.3% of sodium cromoglycate patients and 66.3% of placebo-treated patients. The most frequent adverse effects were transient application site reactions which tended to disappear with increasing duration of treatment, and, less frequently, taste perversion. CONCLUSION: The results of this study indicate that the therapeutic use of azelastine eye drops in patients with seasonal allergic conjunctivitis or rhino-conjunctivitis can be recommended.     

Effect of norepinephrine release on adrenoceptors in severe seizure genetically epilepsy-prone rats

The genetically epilepsy-prone rat (GEPR) seizure model is characterized by extensive abnormalities in brain noradrenergic function. Earlier studies had suggested that GEPRs might not regulate adrenoceptors in a normal fashion. The purpose of the present study was to determine if GEPR-9s are capable of up and down regulation of alpha(1)- and beta-adrenoceptors in response to increments or decrements in extracellular norepinephrine. Seizure induction has been shown to increase extracellular norepinephrine. Chronic sound or electroshock-induced seizures caused down regulation of beta-adrenoceptors in frontal cortex and in hippocampus from GEPR-9s. Similarly, chronic daily treatment with the norepinephrine reuptake inhibitor desmethylimipramine produced down regulation of beta-adrenoceptors in frontal cortex and in hippocampus from GEPR-9s. As is the case in neurologically normal animals, chronic electroshock-induced seizure did not cause down regulation of beta-adrenoceptors in 6-hydroxydopamine pretreated GEPR-9s. Chronic electroshock treatment also caused up-regulation of alpha(1)-adrenoceptors in frontal cortex but not in hippocampus. In 6-hydroxydopamine pretreated GEPR-9s, chronic electroshock treatment caused a further up-regulation of alpha(1)-adrenoceptors in frontal cortex but not in hippocampus. Taken together, these results indicate that GEPR-9s are capable of up and down regulation of alpha(1)- and beta-adrenoceptors in a manner that is qualitatively similar to the regulation of these receptors in normal animals. Whether the regulation of brain adrenoceptors is quantitatively different in GEPRs from normal animals remains to be established.     

Haemophilus influenzae induced loss of lung beta-adrenoceptor binding sites and modulation by changes in peripheral catecholaminergic input

Vaccination of guinea pigs with killed suspensions of Haemophilus influenzae, a bacterium often found in the deeper respiratory airways of asthmatic bronchitics, results in a number of effects suggesting an impairment of beta-adrenoceptor function. A [3H]dihydroalprenolol binding assay was used to determine the number of beta-adrenoceptors (Bmax) following H. influenzae vaccination. The Bmax declined significantly by 29% from 1240 +/- 80 to 880 +/- 70 fmol/mg protein, while the binding affinity of the sites was not changed. Specific binding in the presence of 1.8 nM [3H]DHA to tracheal longitudinal smooth muscle was also significantly lower in H. influenzae-vaccinated animals as compared to controls. Furthermore modulation of peripheral sympathetic input to lung beta-adrenoceptors was evaluated in our model. Pretreatment with Ro4-4602, an inhibitor of dopa-decarboxylase, increased the number of beta-adrenoceptors and prevented the H. influenzae-induced loss of beta-adrenoceptors. On the other hand repeated doses of the antidepressant desipramine mimicked the effect of H. influenzae vaccination i.e. a loss of beta-adrenoceptors. Desipramine and H. influenzae vaccination were not synergistic in their effects. The effects of H. influenzae and modulation of catecholaminergic input on guinea pig lung beta-adrenoceptors were compared with tracheal strip relaxation by isoproterenol, following similar treatments assessed in a superfusion model. Changes in lung beta-adrenoceptor number were almost identical with changes in tracheal strip relaxation. These results suggest that compensatory regulation adapts the number of respiratory beta-adrenoceptors to changes in sympathetic input. A similar mechanism may underlie the loss of beta-adrenoceptors following H. influenzae vaccination.     

Mechanism of the antitussive effect of azelastine in guinea pigs

In order to clarify the mechanism of the antitussive effects of azelastine hydrochloride (azelastine, CAS 790307-93-0), the cough responses to inhaled capsaicin and substance P (SP) were evaluated before and after the administration of azelastine in conscious guinea pigs. The concentrations of SP were also measured before and after the administration of azelastine by radioimmunoassay in anesthetized guinea pigs. Capsaicin and SP caused coughing in conscious guinea pigs in a dose-dependent fashion. After the treatment with azelastine, capsaicin-induced cough decreased significantly, and the dose-response curve to capsaicin was shifted to a higher concentration in comparison with the the controls. SP-induced cough was not inhibited by the treatment with azelastine, and the dose-response curves to SP did not change. The concentrations of SP recovered in bronchoalveolar lavage fluid and in the trachea were decreased statistically significantly in a dose-dependent manner after the treatment with azelastine, while the SP concentrations of the subjects not treated with azelastine were not inhibited. These results suggest that the antitussive effect of azelastine might be partly due to the inhibition of SP release from sensory nerves in guinea pigs.     

氮卓斯汀对豚鼠哮喘的拮抗作用及相关机制

目的:研究组胺H1受体拮抗剂——氮卓斯汀(azelastine,AZT)对豚鼠哮喘的拮抗作用,探讨氮卓斯汀拮抗哮喘的可能机制。方法:以卵白蛋白致敏豚鼠,制备哮喘模型,通过豚鼠引喘潜伏期和跌倒率的变化评价氮卓斯汀对哮喘的拮抗作用;分别计数外周血和支气管肺泡灌洗液(BALF)中嗜酸性粒细胞的数量;采用ELISA法检测血清和BALF中IL-4和IL-5的质量浓度。结果:与模型组相比,氮卓斯汀能显著延长致敏豚鼠的引喘潜伏期,降低跌倒率;氮卓斯汀显著减少哮喘豚鼠血清和BALF中嗜酸性粒细胞的数量,降低血清和BALF中IL-4和IL-5的水平。结论:降低IL-4和IL-5的水平,减少血中嗜酸性粒细胞的数量及其在气道中的浸润,可能是组胺H1受体拮抗剂——氮卓斯汀拮抗哮喘的机制之一。     

Meta-analysis of azelastine nasal spray for the treatment of allergic rhinitis

STUDY OBJECTIVE: To systematically review the efficacy of azelastine nasal spray for the treatment of allergic rhinitis. DESIGN: Meta-analysis of published randomized controlled trials reported in English. DATA SOURCE: Published literature from the PubMed-MEDLINE database. PATIENTS: Patients aged at least 12 (United States) or 16 years (Europe) with allergic rhinitis or nonallergic vasomotor rhinitis. MEASUREMENTS AND MAIN RESULTS: A global assessment of efficacy was used to estimate the number needed to treat for azelastine nasal spray compared with placebo or active comparators. The total symptom score was used to compare the effect size between azelastine and placebo. In five comparisons of azelastine and placebo, azelastine was most efficacious, with a summary number needed to treat of 5.0 (95% confidence interval [CI] 3.3-10.0). In reviewing 11 studies of azelastine versus active comparators, we found no significant difference between azelastine and active comparators (number needed to treat 66.7, 95% CI 14.3 to infinity to 25). Azelastine was more efficacious than placebo in terms of total symptom score (effect size of 0.36, 95% CI 0.26-0.46). CONCLUSION: Azelastine nasal spray was more efficacious than placebo in the treatment of allergic rhinitis. No significant differences were observed between azelastine and active comparators for the treatment of allergic rhinitis; however, when azelastine was compared with oral antihistamines as monotherapy, the trend favored azelastine. Because azelastine appears to be as efficacious as oral antihistamines, the choice of treatment for seasonal allergic rhinitis should depend on the patient's preference regarding the route of administration, adverse effects, and the cost of the drug.     

浓缩秦氏敷贴方中姜酒和敷贴药渣对哮喘豚鼠的作用研究

目的探讨浓缩秦氏敷贴方中的姜酒和其药渣对哮喘豚鼠的影响。方法选用健康♂豚鼠,随机分为5组：传统秦氏敷贴（A）组、哮喘模型（B）组、空白对照（C）组、姜酒敷贴（D）组、药渣敷贴（E）组。采用雾化吸入鸡卵蛋白（OVA）进行攻击,建立哮喘模型。A组敷贴秦氏敷贴剂,B组敷贴生理盐水,C组正常饲养,D组敷贴含药姜酒,E组敷贴药渣。第2周起OVA攻击后敷贴,1周2次。于第1、2、4和8次OVA攻击后进行哮喘症状评分。于第7次敷贴后处死动物,观察肺脏组织经HE染色后肺组织病理学改变及粒细胞计数。结果第4次OVA攻击后,D组哮喘症状减轻,第8次OVA攻击后,A组、E组哮喘症状减轻。各组哮喘豚鼠肺组织中的粒细胞计数均减少。结论姜酒浓缩敷贴提高了传统秦氏敷贴疗效,在敷贴2次后即显示出疗效。药渣敷贴与传统秦氏敷贴疗效相似。     

普米克令舒联合博利康尼治疗慢性喘息型支气管炎急性发作的疗效观察

目的观察普米克令舒联合博利康尼雾化治疗慢性喘息型支气管炎急性发作的临床疗效与安全性。方法将80例慢性喘息型支气管炎随机分为两组,普米克令舒联合博利康尼雾化治疗组及对照组,两组基础药物相同,对两组的血气、激素用量、机械通气使用率、疗效及副作用等进行评价。结果治疗组于治疗后1d、5d动脉血气分析指标、激素用量、机械通气使用率、临床控制+显效率明显优于对照组(P<0.01)。治疗组无1例出现副作用。结论普米克令舒联合博利康尼雾化能明显改善喘息症状,降低全身糖皮质激素用量,减少机械通气使用率,无明显不良反应。     

Regulation of beta 1- and beta 2-adrenoceptors following chronic treatment with beta-adrenoceptor antagonists

The effect of chronic pretreatment of guinea pigs with various beta-adrenoceptor antagonists on the binding characteristics of the radioligand 125I-cyanopindolol (ICYP) and responsiveness of adenylate cyclase to isoprenaline in the gastrocnemius muscle (beta 2-adrenoceptors) and the left ventricle (beta 1-adrenoceptors) were compared. Pretreatment of guinea pigs with propranolol or ICI 118,551 for one week significantly increased the density of the beta 2-adrenoceptors in the gastrocnemius muscle. Atenolol pretreatment for one week did not affect the density of the receptors. Pretreatment of the animals with pindolol for one week reduced the density of beta 2-adrenoceptors in skeletal muscle. In the left ventricle pretreatment of the guinea pigs with any of the antagonists did not alter either the density or the KD of beta 1-adrenoceptors. The responsiveness of adenylate cyclase to isoprenaline (10(-4) M) in the left ventricle or skeletal muscle was not affected when the guinea pigs were pretreated with propranolol. Pretreatment of the guinea pigs with reserpine (0.5 mg.kg-1) intraperitoneally for one week, to deplete catecholamines did not affect beta-adrenoceptor density or KD in the left ventricle or skeletal muscle. We conclude that the regulation of beta-adrenoceptors by the antagonist may not be caused by the prevention of the access of endogenous agonists to beta-adrenoceptors and it is dependent on the selectivity of the antagonist and on the susceptibility of the receptors to regulation.     

布地奈德混悬液联合硫酸特布他林雾化吸入治疗AECOPD30例临床观察

目的研究布地奈德混悬液联合硫酸特布他林雾化吸入对慢性阻塞性肺病急性加重期（AECOPD）的临床疗效。方法对60例AECOPD住院患者随机分为观察组与对照组。观察组30例,在常规治疗的基础上给予布地奈德混悬液2mg和硫酸特布他林雾化液5mg加生理盐水2ml联合雾化吸入治疗,2次/d;对照组30例,在常规治疗的基础上给予给以硫酸特布他林雾化液5mg加生理盐水2ml治疗,2次/d,对两组患者用药7d后的临床症状、血气分析及第一秒用力呼气容积占预计值百分比（FEV1%预计值）变化情况进行比较分析。结果两组治疗前后PaO2、PaCO2、FEV1%预计值比较,差异有统计学意义（P〈0.05）,两组间各对应指标相比较,差异均有统计学意义（P〈0.05）。两组的年龄、性别、发病、病程等构成情况大致相同。结论布地奈德联合硫酸特布他林雾化吸入对AECOPD能迅速缓解病情,畅通呼吸道,改善肺功能,疗效优于单一用药,是治疗AECOPD的有效选择。     

Effect of azelastine hydrochloride on vascular permeability in hypersensitivity reaction skin site in guinea pig

4-(p-Chlorobenzyl)-2-(hexahydro-1-methyl-1H-azepine-4-yl)-1-(2H)-phthalazinone hydrochloride(azelastine) is a new compound promising anti-allergic effect, which was tested on increased vascular permeability in two types of hypersensitivity skin reaction in guinea pigs. The reversed passive Arthur (RPA) reaction was induced by bovine serum albumin and its heterologous or homologous antibody IgG. A monophasic permeability response, shown by amount of extravasated Evan's blue, was considerably suppressed by pretreating the animals orally with azelastine at different concentrations. In contrast, antihistamines such as triprolidine, chlorpheniramine and pyrilamine had no effect on the vascular response. Thus the potent antiexudative action of azelastine was demonstrated for the RPA reactions in guinea pigs as the model. However, the vascular response in tuberculin reaction in guinea pigs was not influenced by azelastine suggesting a different permeability mechanism.     

The Gln27Glu beta2-adrenoceptor polymorphism slows the onset of desensitization of cardiac functional responses in vivo

Studies performed have shown that the Arg16Gly allele in beta-adrenoceptors (beta2AR) enhances susceptibility to agonist-induced down-regulation, while the Gln27Glu polymorphism diminishes it. In this study, we tested whether similar phenotypes occur in vivo. We assessed 32 volunteers (mean age 25 +/- 2 years) with different genotypes (group A: wild-type beta2AR, n = 16; group B: homozygous Glu27, n = 10; group C: homozygous Gly16, n = 6) for the effect of 2 weeks treatment with 3 x 5 mg/day oral terbutaline on terbutaline infusion-induced increases in heart rate and contractility (i.e. shortening of heart rate-corrected duration of electromechanical systole, QS2c). At baseline, terbutaline infusion increased heart rate and contractility similarly among subjects in the three groups. Treatment with oral terbutaline for 14 days reduced the ability of intravenous (i.v.) terbutaline to increase heart rate and contractility. The extent of this reduction was similar but the time course of desensitization differed among the three groups. While in groups A and C terbutaline infusion-induced increases in heart rate and contractility were reduced within 24 h after oral ingestion of terbutaline, a significant effect on response to terbutaline infusion was not evident for the first 3 days of terbutaline treatment in group B. The Arg16Gly and the Gln27Glu variants of the beta2AR do not alter the extent of agonist-induced beta2AR desensitization in vivo but Glu27 homozygotes develop desensitization more slowly. This result may have implications for cardiac side-effects in patients who are Glu27 homozygotes and who receive beta2AR agonist therapy.     

布地奈德联合特布他林雾化吸入治疗毛细支气管炎162例疗效观察

目的：观察布地奈德联合特布他林雾化吸入治疗毛细支气管炎的临床疗效。方法：将162例毛细支气管炎患儿以随机抽样法分成对照组80例和治疗组82例。2组患者均常规给予抗感染、抗病毒、平喘、化痰、吸氧等治疗,治疗组在此基础上加用布地奈德混悬液联合特布他林雾化液气泵雾化吸入,比较2组疗效并进行统计学处理。结果：治疗组患者在咳嗽消失、喘憋缓解、哮鸣音和肺部哆音消失时间、病程缩短方面明显优于对照组（P〈0．01）;治疗组（治愈率为93．90％）疗效优于对照组（治愈率为61．25％）（P〈0．01）。结论：布地奈德联合特布他林雾化吸入治疗毛细支气管炎疗效好,值得临床推广。     

Comparison of the efficacy and tolerability of topically administered azelastine,sodium cromoglycate and placebo in the treatment of seasonal allergic conjunctivitis and rhino-conjunctivitis

SUMMARY

Objective and setting: Azelastine (AZE) in a novel, eye drop, formulation, was compared with topically applied sodium cromoglycate (SCG) and placebo (PLA) in the treatment of seasonal allergic conjunctivitis or rhino-conjunctivitis in a multicentre, parallel group study.

Research design: 144 subjects ranging in age from 16 to 65 years participated. All had at least a 2-year history of seasonal allergic conjunctivitis and were symptomatic at the time of inclusion.

Medications were administered topically either twice daily (AZE/PLA) or four times daily (SCG) over a 2-week treatment period.

Method and outcome measures: Azelastine and placebo were compared double-blind; the comparison versus SCG was carried out in an open manner. Itching, redness, flow of tears, eyelid swelling, foreign-body sensation, photophobia, soreness and discharge were scored on a 4-point severity scale.

Results: Results for the decrease of main conjunctivitis symptoms (itching, tearing and conjunctival redness) showed a marked effect for both active treatments on day 3 with a sustained improvement on days 7 and 14. A clear response to treatment (an improvement of sum scores for day 3 of >3 points compared to baseline) occurred in 85.4% of azelastine-treated patients, 83.0% of sodium cromoglycate patients and 56.3% of placebo patients. Response rates for both active treatments were statistically superior to those for placebo (azelastine p?=?0.005; sodium cromoglycate p?=?0.007). Global assessment of efficacy was at least 'satisfactory' for 90.0% of azelastine patients, 81.3% of sodium cromoglycate patients and 66.3% of placebo-treated patients. The most frequent adverse effects were transient application site reactions which tended to disappear with increasing duration of treatment, and, less frequently, taste perversion.

Conclusion: The results of this study indicate that the therapeutic use of azelastine eye drops in patients with seasonal allergic conjunctivitis or rhino-conjunctivitis can be recommended.     

Birth insult alters dopamine-mediated behavior in a precocial species, the guinea pig. Implications for schizophrenia.

Schizophrenia is associated with increased birth complications, suggesting that birth complications might alter CNS dopaminergic activity later in life. In rats, Caesarean section (C-section) birth can produce long term changes in dopaminergic biochemistry and behavior. However rat brain is somewhat immature compared to human brain at birth. The current study tested if mild birth complications also alter dopamine-mediated function in a species with a more mature CNS at birth, the guinea pig. As adults, guinea pigs born by C-section showed increased amphetamine-induced locomotion and disruption of prepulse inhibition (PPI) of acoustic startle, compared to vaginally born controls. Guinea pigs born by C-section with 1 min of added global anoxia showed reduced amphetamine-induced locomotion and disrupted PPI, while a C-section plus 2 min anoxia group showed no change in amphetamine-induced locomotion but increased amphetamine-induced startle. No group differences in effects of amphetamine or apomorphine on PPI were observed. Taken with previous findings, these results indicate that mild birth complications can cause long term changes in dopamine-mediated behavior in both guinea pig and rat, two species spanning the level of human brain maturity at birth.