Postnatal administration of two peptide solutions affects passive avoidance behaviour of young rats.

The effects of two subcutaneously injected peptide solutions CERE (100 mg/kg b. wt.) and E021 (1 mg/kg b. wt.) and of 0.9% saline on passive avoidance reaction (PAR) of young rats were examined. Animals were trained and tested in a step-through avoidance task using a footshock of 0.5 mA or 1 mA. Step-through latencies were observed up to 200 s and from these data the percentage of good learners (latency = 200 s) and bad learners (latency < 200 s) was calculated. Two experimental schedules were performed (n > 6). In Expt. 1 rat pups were chronically treated with the substances within the first 7 days after birth. In Expt. 2 the 7 days of treatment started in the 4th postnatal week. In both experiments PAR acquisition was trained on the 28th day after birth (learning trial), PAR extinction testing started on the 29th day (retention trials). After applying a 0.5-mA footshock, rat pups treated with E021 within the first 7 days of life (Expt. 1) displayed significantly slower PAR extinction when compared to saline- and CERE-treated rats. In the 1 mA groups, significant differences in step-through latencies were measured between 0.9% saline- and E021-pretreated animals on retention day 11 and between saline and CERE on retention days 9 and 13. E021-treated rats of Expt. 2, receiving a footshock intensity of 0.5 mA, showed significant lower step-through latencies when compared to E021-treated rats of Expt. 1. In Expt. 2 no significant differences between treatment groups were observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of atrial natriuretic peptide on passive avoidance behaviour in rats.

The effects of rat atrial natriuretic peptide (ANP 1-28) on passive avoidance behaviour were tested following its administration into the lateral brain ventricle in rats. Different doses of ANP 1-28 were administered immediately after the learning trial of passive avoidance behaviour and the effects on the consolidation of learning were tested 24 h later. ANP 1-28, in doses in the range 50-2000 ng/rat, caused a dose-dependent increase in passive avoidance latency. Selected doses (100, 200 and 500 ng/animal) were given 30 min before the learning trial. These doses lengthened the passive avoidance latency in a dose-dependent manner. When the peptide was given 30 min before the retention trial, there was no significant alteration in passive avoidance response. The data suggest that ANP 1-28 is able to facilitate the learning and consolidation of fear-motivated passive avoidance behaviour.     

Modulation of passive avoidance behavior of rats by intracerebroventricular administration of cholecystokinin antiserum

The effects of intracerebroventricular administration of two different cholecystokinin antisera were tested on the latency of passive avoidance behaviour of rats following 6, 12, 24, 48, 72 and 96 h retention. In a 1:2 dilution, both CCK antisera caused a shorter latency than in the controls following 6, 12, 24 and 48 h retentions. These data suggest that the endogenous CCK of the brain might be a physiologic modulator of memory processes.     

Antinociceptive profile of intracerebroventricular salmon calcitonin and calcitonin gene-related peptide in the mouse formalin test

The effects of intracerebroventricularly administered salmon calcitonin (sCT) and calcitonin gene-related peptide (CGRP) on the behavioural response of the mouse to formalin injections were investigated. Mice lick their hindpaws for 5 min after formalin injections, then stop, and resume intensive licking for another 10 min beginning 20 min after the injections. Both peptides reduced the nociceptive response in the two phases of the test (0-5 and 20-30 min after formalin injection). Antinociceptive A50 values were 3.3 micrograms/mouse and 4.7 micrograms/mouse respectively in the first phase for sCT and CGRP. The effects of sCT and CGRP appeared to be dose-dependent in the first phase. Since in the second phase sCT appeared more effective and CGRP gave a bell-shaped curve, possible differences in the mechanisms of action of the peptides in the two response intervals of the test are suggested.     

Effects of postnatal stimulation on the passive avoidance behaviour of young rats

We examined the effects of stimulation on either postnatal days 1–7 or 21–27 on passive avoidance reaction (PAR) of young rats. Animals received tactile or visual stimulation for 10 min each day, and were trained on postnatal day 28 in a step-through apparatus using a footshock of 0.75 mA for 2 s. Retention was tested on five consecutive days beginning on day 29. Memory retention was measured for each rat 24, 48, 72, 96 and 120 h after the acquisition trial. Step-through latencies to enter the dark compartment, time spent in the illuminated compartment and number of crossings of the light beam were recorded up to 200 s. Rats that received tactile or visual stimulation during the 4th postnatal week displayed significantly lower PAR latencies, a shorter stay in the illuminated compartment and a higher number of crossings of the light beam compared to rats treated during the 1st postnatal week. The untreated control group showed a rapid decline of PAR latencies. All experimental groups remained in the illuminated compartment longer and showed PAR latencies well above those of the control group. The differences became more pronounced when visual stimulation in the first postnatal week was used. The number of crossings of the light beam was significantly reduced by the treatment, with the exception of the experimental group stimulated visually in the 4th week. The behavioural changes induced by tactile or visual stimulation have a long-lasting effect in coping with a stressful task.     

Neonatal administration of vasopressin antiserum induces long-term deficits on active and passive avoidance behaviour in rats

Two-day-old male rats received a subcutaneous injection of arginine-vasopressin (AVP) antiserum and avoidance behaviour was studied 3 months later. Rats treated with the antiserum showed a clear retention deficit in a one-trial learning, step-through passive avoidance situation. Anti-AVP treatment also induced an impairment on the acquisition of a two-way active avoidance task. Systolic blood pressure was lower than normal in these animals. The results obtained appear to be indicative of the high vulnerability of the developing nervous system, and are discussed in the context of the different hypothesis on the role of central or peripheral mechanisms in the behavioural effects of AVP. Although no definite conclusions may be drawn in this regard, the present data strongly suggest that neonatal administration of AVP antiserum exerts long-lasting effects upon the functionality of several physiological mechanisms related to the behavioural adaptation of the organism.     

Effects of calcitonin gene-related peptide and vasoactive intestinal peptide on nicotine-induced sweating in man

The effects of two neuropeptides, calcitonin gene-related peptide and vasoactive intestinal peptide on nicotine-induced sweating in human skin were investigated. Intradermal injection of nicotine induced local sweating and each peptide, administered together with nicotine, inhibited these responses in a concentration-dependent manner. The concentration of calcitonin gene-related peptide for threshold and half-maximum inhibition were about 10(-10) M and 10(-8) M, respectively, while those of vasoactive intestinal peptide were approximately 10(-9) M and 10(-7) M, respectively. The results suggest that calcitonin gene-related peptide and vasoactive intestinal peptide have inhibitory effects on the nicotinic action, and release of endogenous calcitonin gene-related peptide and/or vasoactive intestinal peptide may influence sweating in human skin under physiological conditions in vivo.     

Effects of intracerebroventricular administration of ultra low doses of histaminergic drugs on morphine state-dependent memory of passive avoidance in mice

The effects of intracerebroventricular (i.c.v.) administration of ultra low doses (ULDs) of histamine, clobenpropit and pyrilamine are studied on morphine state-dependent (STD) memory in mice. Although pre-test administration of different doses of histamine and clobenpropit showed no effect on impairment of memory induced by pre-training morphine, when the above drugs were co-administered with morphine, they inhibited the restoration of memory by morphine. These effects were opposite to microgram doses of the same drugs.     

Modulation of passive avoidance behaviour by cholecystokinin octapeptides in rats

The effects of two different doses of cholecystokinin octapeptide sulphate ester and its unsulphated form on the passive avoidance behaviour were studied following intraperitoneal administration to rats. Administered immediately after the learning trial in a dose of 400 nmole/kg, both peptides resulted in significantly increased passive avoidance latencies as compared to the control. There were no effects on the latency of passive avoidance behaviour when the animals were treated 1 h before the learning trial. When the cholecystokinin octapeptides were given 23 h after the learning trial, the latency tended to be increased, but this difference was not statistically significant.     

Effects of intracerebroventricularly administered somatostatin on passive avoidance, shuttle-box behaviour and open-field activity in rats

Behavioural effects of somatostatin after intracerebroventricular (icv) administration have been investigated in male rats. In a passive avoidance learning test, somatostatin (1 microgram), given 30 min before the learning session, increased the avoidance latency at 24 h, but not at 48 h, after the injection, when compared to a 10 micrograms treated group. However, compared to a saline treated group, somatostatin (0.01, 0.1, 1, or 10 micrograms) did not significantly influence the avoidance latency. In a shuttle box experiment somatostatin (1 microgram) facilitated the learning process. In an open-field behaviour test, immediately after the 24 h passive avoidance test, 10 micrograms of the peptide decreased the rearing activity without influencing other open field behaviours, like locomotion, grooming and defecation. In a second open-field experiment somatostatin (1 microgram), given 30 min prior to the test, similarly as in the shuttle box learning experiment, increased the locomotion of the animals. These data suggest that somatostatin influences both the passive avoidance and shuttle box behaviours. The peptide-induced motor performance of the animals may play an important role in influencing the responses observed in these behavioural tests.     

Effects of nitric oxide on passive avoidance learning in rats

To investigate the effects of nitric oxide (NO) on passive avoidance learning, L-NAME, D-NAME, and L-arginine were administered i.p. 30 min prior to learning trial; the effects of these substances were tested 24 h later using a passive avoidance apparatus in rats. To reveal the effect of NO on consolidation of acquired memory, L-NAME, D-NAME, and L-arginine were administered i.p. immediately after learning trials and animals were tested 24 h later. Effect of NO on retention was also investigated by injecting L-NAME, D-NAME, and L-arginine (same dosages) 30 min prior to 24 h testing (retrieval). L-NAME administered 30 min before and 24 h after learning trial significantly decreased the avoidance latency but there was no significant effect on consolidation. L-Arginine appeared to enhance the retention of acquired memory significantly, whereas D-NAME had no effect on any testing regime. The results suggest that NO may be involved in learning and retention of passive avoidance.     

Effects of intracerebroventricular administration of ovine corticotropin-releasing factor (CRF 1-41) on passive avoidance behaviour: lack of influence on monoamine contents of limbic brain areas

The effects of intracerebroventricular administration of synthetic ovine corticotropin-releasing factor (CRF 1-41) have been investigated on the retention of passive avoidance behaviour, and on the dopamine, norepinephrine and serotonin contents of the hypothalamus, mesencephalon, amygdala, septum and striatum, as well as on the plasma corticosterone levels of hypophysectomized and sham-operated rats. Treatment with CRF 1-41 20 min before the first retention test, 24 hours after the learning trial, significantly facilitated the passive avoidance behaviour of hypophysectomized animals in a dose-dependent manner. No effect was found in sham-operated rats. No significant effects of a wide dose range of intracerebroventricularly injected CRF on the monoamine contents of limbic brain structures were detected. However, the same doses of CRF 1-41 increased the plasma corticosterone level in sham-operated rats. The data suggest that the release of CRF from neurons in the limbic system does not alter the monoamine contents in this system, although this peptide facilitates the retention of the passive avoidance behaviour of hypophysectomized rats.     

Effects of tifluadom on passive avoidance behaviour in DBA/2 mice

The effects of the selective opiate kappa-receptor agonist tifluadom on memory were investigated in a passive avoidance task in 3 sets of experiments carried out with DBA/2 (DBA) mice both familiarized and unfamiliarized with the apparatus. In a first set of experiments, tifluadom (1.0 or 2.5, but not 0.5 mg/kg) administration immediately after training impaired retention performance of non-familiarized mice. This impairment was still evident when the drug was injected 15 or 30, but not 60 min after training. A second set of experiments was carried out with mice familiarized with the apparatus. Tifluadom was less effective in impairing memory in this group of animals, as compared with non-familiarized mice. Finally, in a third set of experiments, carried out with non-familiarized mice, a 15 min immobilization stress, which was ineffective when administered alone, enhanced the effects of tifluadom (1.0 mg/kg). The results are discussed in terms of attenuation of emotionality, resulting in impaired retention, following post-training opiate administration.     

降钙素基因相关肽神经生长因子与失神经支配兔骨折愈合

背景：骨折不愈合严重影响患者生活质量,神经生长因子用于骨不连的防治是重建外科领域研究的重点和方向。 目的：观察神经生长因子降钙素基因相关肽对失神经支配兔骨折愈合的影响。 方法：构建大白兔失神经支配腓骨骨折模型后,实验组骨折端局部注射降钙素基因相关肽10 μg,每2 d一次;对照组骨折端局部注射等量生理盐水。术后2,4,6周分别测定静脉血中肾上腺素和去甲肾上腺素的水平,并进行生物力学和组织学分析。 结果与结论：术后两组血清肾上腺素和去甲肾上腺素水平均有显著增高,在术后第4周达到最高峰,比术前高出1倍以上,第6周时出现下降,但仍然显著高于术前;术后2,4,6周,实验组肾上腺素和去甲肾上腺素血清水平较对照组显著增高,差异具有显著性意义(P < 0.05~0.01)。在三点弯曲实验中,实验组骨痂的抗弯强度明显高于对照组(P < 0.05~0.001);术后第6周时苏木精-伊红染色可见实验组骨痂中的透明软骨细胞已被成骨细胞替代,对照组骨痂中的软骨细胞仍没有完全成骨细胞化。提示神经生长因子降钙素基因相关肽对失神经支配兔骨折愈合具有明显的促进作用。 关键词：神经生长因子;降钙素基因相关肽;骨折愈合;生物力学;生物化学     

Biphasic effects of orchidectomy on calcitonin gene-related peptide synthesis and release.

We hypothesize that the decline of male gonadal hormones may play a role in age-related decrease of calcitonin gene-related peptide (CGRP) synthesis and release. Orchidectomized rats were raised with or without testosterone replacement and CGRP levels in serum and some tissues as well as the perfusate from the isolated mesenteric arterial bed (MAB) were measured at 1, 2 and 4 months after orchidectomy. CGRP levels of serum and tissues, and CGRP release from MAB were significantly elevated after 1 month and decreased after 4 months in orchidectomized rats. The changes were restored by testosterone replacement. Our results indicate that the age-related decline of testosterone might contribute to the age-related decrease of CGRP synthesis and release.     

大鼠松质骨中降钙素基因相关肽在脊髓损伤后的变化

背景：细胞因子异常及神经功能的异常、激素水平的改变均参与了脊髓损伤后骨质疏松的发生，以往对细胞因子及激素改变的研究较多，而对神经异常对骨调节的研究相对较少。 目的：课题创新性地应用血生化与免疫组织化学相结合的方法，观察脊髓损伤后大鼠松质骨中神经多肽降钙素基因相关肽的变化，分析其在脊髓损伤后骨质疏松中的意义。 设计、时间及地点：随机对照动物实验，于2008-09/12在解放军第四军医大学骨科研究所实验室完成。 材料：3月龄SD大鼠48只，体质量为(210±16) g，随机均分为脊髓损伤组与对照组，每组24只。 方法：脊髓损伤组于T10处完全横断脊髓；对照组仅行椎板切除术。 主要观察指标：术后1，3，6 周分批每组随机取8只动物处死。测定血骨特异性碱性磷酸酶、Ⅰ型胶原氨基末端肽；对股骨髁松质骨行降钙素基因相关肽免疫组织化学染色,结合计算机图像分析系统对降钙素基因相关肽免疫阳性神经的染色强度进行定量分析。 结果：脊髓损伤组各时间段血清Ⅰ型胶原氨基末端肽浓度显著高于对照组(P < 0.05或0.01)，各时间段血清骨特异性碱性磷酸酶活性低于对照组，但差异无显著性意义(P > 0.05)。对照组各时间段分布于小梁骨内的降钙素基因相关肽免疫阳性神经呈强阳性，脊髓损伤组降钙素基因相关肽较对照组减弱( P < 0.05或0.01)。 结论：脊髓损伤后松质骨内降钙素基因相关肽的减弱可能与脊髓损伤后骨质疏松的发生有关。     

Hypoprolactinemic effect of calcitonin gene-related peptide in the rat

The effect of calcitonin gene-related peptide (CGRP) on prolactin (PRL) secretion was studied in female rats. Prepubertal female rats were submitted to the stressful stimuli of injection, blood puncture and thermal stress. Lactating rats were exposed to suckling stimulus. The effects of CGRP on PRL release were compared to those of calcitonin (CT). CGRP i.p. or s.c. prevents the increase in circulating PRL induced by stress. This effect was observed two hrs and even 24 hrs after CGRP administration. It was elicited at all doses tested, 2.5, 1.25 and 0.6 micrograms per animal. The time course of the actions of CGRP and CT are different. It is proposed that CGRP and CT act on different receptors.     

Direct androgenic regulation of calcitonin gene-related peptide expression in motoneurons of rats with mosaic androgen insensitivity.

The spinal nucleus of the bulbocavernosus (SNB) and its target muscles, bulbocavernosus and levator ani (BC/LA), form a sexually dimorphic neuromuscular circuit whose development and maintenance are androgen-dependent. The mechanisms whereby androgen regulates gene expression in the SNB of adult rats are largely unknown, although a retrograde influence from the BC/LA muscles has been suggested to underlie the suppression of calcitonin gene-related peptide (CGRP) expression observed in SNB motoneurons after systemic androgen treatment. A mosaic paradigm was used to determine the site of action of androgen in the regulation of CGRP expression in SNB motoneurons. As a consequence of random X chromosome inactivation, androgenized female rats heterozygous for the tfm androgen receptor (AR) mutation (XwtXtfm-mosaics) express a mosaic of androgen-sensitive and androgen-insensitive motoneurons in the SNB, whereas the BC/LA target musculature appears to be uniformly sensitive to androgens. In adult mosaics, testosterone administration resulted in a reduction in the proportion of androgen-sensitive cells expressing CGRP, whereas no such reduction was observed in the androgen-insensitive population, indicating that neuronal AR plays an essential role in the neuromuscular regulation of CGRP expression in these motoneurons. This provides the first in vivo demonstration of AR regulation of gene expression unambiguously localized to a neuronal population.     

Antinociceptive effects of calcitonin gene-related peptide injected into periaqueductal grey of rats with mononeuropathy

Intra-periaqueductal grey (PAG) injection of calcitonin gene-related peptide (CGRP) induced dose-dependent increases in hindpaw withdrawal latency (HWL) to thermal and mechanical stimulation in rats with mononeuropathy. CGRP-induced increases in HWLs were blocked by intra-PAG injection of the CGRP antagonist CGRP8-37. The results demonstrated that CGRP and CGRP receptors in PAG play an important role in antinociception in rats with mononeuropathy.