Physiology and Pharmacology
Volume:15 Issue: 2, 2011

Gonadotropin inhibitory hormone (GnIH) is believed to be an inhibitor of gonadotropin releasing hormone (GnRH) secretion. The role of GnIH in lactational inhibition of gonadotropin secretion is not well known; therefore, the aim of the present study was to evaluate the effect of lactation on expression of GnIH in these nuclei of lactating and non-lactating rats.

Ten postpartum rats of the Sprague-Dawley strain were randomly allotted into two groups. The number of pups was adjusted to five pups per suckling female, while the control non-lactating rats were separated from their pups immediately upon parturition. The lactating rats were allowed to suckle their pups for eight days. The number of GnIH neurons in the dorsomedial (DMH) and paraventricular (PVN) nuclei was estimated using an immunohistochemical method.

The number of GnIH neurons in DMH (P=0.005) and PVN (P=0.001) of lactating rats were significantly higher than those of the non-lactating rats. Moreover, fibers of GnIH neurons were observed in anteroventral periventricular nucleus (AVPV) in lactating rats.

Lactation increased GnIH expression in DMH and PVN of the lactating rats, and thus may have a role in inhibiting GnRH and subsequently LH secretion during the lactation period.

Developmental changes in atrioventricular nodal conduction time and refractoriness have been shown in several studies. Prevalence of atrioventricular nodal reentrant tachycardia (AVNRT) is clearly age-dependent. The purpose of this study was to determine developmental changes of basic and frequency-dependent electrophysiological properties of the atrioventricular node (AV-node) in neonatal and adult rabbits. In this study, the effects of increasing age on the basic and rate-dependent properties of isolated perfused AV-node were analyzed in neonatal (2-week-old) and adult (12-week-old) New Zealand rabbits. Specific stimulation protocols of recovery, facilitation and fatigue were separately applied in each group (n=7). Unipolar extracellular field potential was recorded by a silver electrode (100 M). The results showed that the basic nodal properties (ERP, FRP, WBCL and AHmax) were significantly shorter in neonates compared to the adult group. The magnitude of fatigue was also decreased in the neonatal group compared to control (18.9 ±3.3 vs. 11.1 ± 1.2 msec). Time constant of recovery of the adult group was significantly higher than the neonatal group (P<0.05). The results of this study showed that nodal basic and frequency-dependent properties are age-related and different developmental changes of slow and fast pathways are responsible for this behavior and may reveal the grater susceptibility of AVNRT in young adults compared to infants.

Thyroid hormones play an important role in the regulation of metabolism, maturity and reproduction. Thyroid dysfunction affects almost all endocrine glands such as pituitary and testis. The aim of this study was to investigate alterations of testosterone and luteinizing hormone (LH) serum levels as well as weights of thyroid gland and testes in methimazole (MMI)-induced hypothyroidism. Twenty-one adult male rats weighing 185 g were divided into 3 groups. The control group received drinking water, while treated groups received two doses of methimazole; low dose (20 mg/dl in drinking water) and high dose (100 mg/dl in drinking water), for 42 days. At the end of the experiments, rats were anesthetized and sacrificed and serum samples were obtained. Serum levels of hormones were measured by radioimmunoassay. Weights of testes and thyroid gland were determined after sacrifice. Results showed that the use of methimazole decreased serum levels of T4, T3, testosterone and LH as well as the weight of testes, while it increased the weight of thyroid gland compared to control group. These effects were more clear in the high dose group. This study suggests that MMI–induced hypothyroidism causes a significant decrease in serum levels of thyroid hormones, testosterone and LH. Hypothyroidism also decreases the weight of testes, while it increases the weight of thyroid in rat. These effects were dose-dependent.

Gestational stress can lead to cerebral functional disorders, such as epilepsy, probably due to the disturbance in the cerebral maturation and causing abnormal neuronal correlations. In the present study, effect of gestational Predator Stress on the neonatal epileptic behaviors was investigated in rats. Female rats (200 ± 20 g) were divided into two groups; intact pregnant rats (control group) and stressed pregnant rats (stressed group). In the stressed group, on gestational days 15, 16, and 17, caged rats were exposed to the cage of a cat for 2 h, once a day. On postnatal day 25, pilocarpine (150 mg/kg s.c.) was injected to pups of both groups, to induce seizure. Then, epileptic behaviors of each pup was observed and recorded. Mean duration of onset of the first neonatal epileptic behavior of the control group was 5.35 ± 0.57 minutes which was decreased to 3.18±0.24 minutes in the stress group. The mean duration of tonic-clonic attacks was significantly increased from 0.53 ±0.1 minute in the control group to 16±3.8 minutes in the stressed group. Moreover, mortality rates during attacks and the level of corticosterone hormone in both mothers and pups showed a significant increase in the stressed group in comparison to the control. Gestational stress can enhance epileptic behaviors in the offspring of rats. Further investigation is required to clarify the underlying mechanism.

Gonadotropin inhibitory hormone (GnIH) and Agouti-related peptide (AgRP) are orexigenic peptides expressed in the arcuate nucleus (Arc) of the hypothalamus in the ewe. In addition, effects of GnIH and AgRP on the regulation of gonadotropin releasing hormone secretion have been shown in some mammals. The objective of the present study was to investigate the coexpression of GnIH and AgRP in Arc of the ewe hypothalamus. Nine ewes were divided into follicular, luteal, and ovariectomised groups (n = 3 each group) and the number of neurons that express GnIH and AgRP and the percentage of coexpression of these two peptides in the Arc of each group was estimated by using immunohistochemistry. In different ovarian conditions of ewes, 19 to 32 percent of GnIH and AgRP neurons were coexpressed in the Arc of the hypothalamus. Results of the present study showed a possible cooperative role of AgRP and GnIH in the Arc of the hypothalamus in regulation of ovarian function in ewe.

According to previous studies, colchicine causes neuronal destruction and learning depression. In this project, effects of colchicine injection into the CA1 and interaction between colchicine and nitric oxide (NO) in this area on the expression of drug-seeking behavior were investigated.

Wistar rats (250-300 g) were bilaterally cannulated at the CA1 area. Colchicine (2-8 μg/rat) was bilaterally administered after the placement of the cannulas and the treated animals were then allowed to recover for about 1 week before behavioral measurements began. Place conditioning was induced by morphine (2.5-5 mg/kg/day, s.c.) and conducted using a five-day schedule of an unbiased task including familiarization, conditioning and testing. NO agents were injected into the CA1 on the day of the testing and the data were analyzed by ANOVA after reviewing the data recorded by Ethovision.

Colchicine significantly reduced the drug-seeking behaviors but morphine caused an increase in these behaviors of colchicine treated rats. NO agents did not show any significant effect except for the compartment entering.

Colchicine may decrease the CA1 neural cell population but morphine increases the signs through a mechanism, which is probably dopamine dependent. The NO agents may produce the effects by dopamine due to induction of morphine.

It has been shown that orexin peptides have a role in opioid withdrawal behaviors. Orexin-expressing neurons that are present in the hypothalamic nuclei send dense projections to the Locus Coeruleus (LC). Withdrawal syndrome is temporally associated with hyperactivity of LC neurons. However, LC neurons do not show withdrawalinduced hyperactivity in the brain slices from morphine-dependent rats. Thus, it has been suggested that the increase in LC neuronal activity seen in vivo is mediated by extrinsic factors. Therefore, this study was carried out to find whether LC microinjection of orexin-A can induce withdrawal behaviors. Adult male Wistar rats weighing 250-300 grams were rendered morphine dependent by subcutaneous injection of morphine sulfate (10 mg/kg) at an interval of 12 h for 9 days. On day 10, intra-LC microinjection of orexin- A (100 μM, 200 nl) was performed two hours after morphine administration. Thereafter, somatic signs of withdrawal were evaluated in a Plexiglas chamber (30 cm diameter, 50 cm height) during a period of 25 min. Orexin-A induced several signs of morphine withdrawal including chewing, scratching, rearing, teeth chattering, wet-dog shake and paw tremor. Acute LC microinjection of an orexin type 1 receptor antagonist, SB- 334867-A, prior to orexin-A prevents the expression of these signs. It may be concluded that orexin, via orexin type 1 receptor at LC acts as an extrinsic factor in the expression of morphine withdrawal syndrome.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease. In the present study, we investigated the response of subventricular zone (SVZ) adult stem cells in the experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and also the differentiation fate of these stem cells. Mice were immunized with MOG peptide emulsified in complete Freund's adjuvant (CFA) and pertussis toxin (PT). Control mice received CFA and PT. To study SVZ stem cells migration, mice received seven i.p. injections of BrdU at 2-h intervals on the day before EAE induction. Demyelination was studied using specific staining with luxol fast blue. The number of BrdU+ cells in SVZ and olfactory bulb (OB) was counted using immunohistochemical staining. To understand the fate of the stem cells, NG2 marker was used to detect oligodendrocyte precursors. Lumbar spinal cord of EAE animals showed significant demyelination and the volume of demyelinated areas was increased on days 14 to 21 post lesion. In the EAE group, more Brdu+ cells were observed in the OB compared to the SVZ. The number of Brdu+/NG2 + cells in OB was significantly increased after EAE induction. The demyelinating context of EAE promotes the migration of SVZ stem cells to the OB. These cells mostly differentiate to oligodendrocyte precursors and may contribute to myelin repair.

It has been reported that traumas such as transverse abdominal incision before myocardial ischemia result in a significantly decreased infarct size. This phenomenon is named remote preconditioning of trauma. Since small skin burn is one of most common traumas, the effect of this injury on ischemia-induced arrhythmias and infarct size was investigated in a rat model of ischemia-reperfusion injury. Twenty-four male Wistar rats were randomly assigned to 3 groups. In burn and sham groups, less than 1% of total body surface area of the dorsal skin was exposed to 100 ˚C and 37 ˚C water, respectively. In ischemic preconditioning group, rats were exposed to one cycle of ischemia (5 min) and reperfusion (10 min). Ischemiareperfusion injury was induced with occlusion and release of left coronary artery for 30 and 120 min, respectively. Infarct size was measured using triphenyl tetrazolium chloride staining and arrhythmias were assessed in accordance with Lambeth conventions. Infarct size was significantly reduced in ischemic preconditioning group compared with the sham group (27 ± 2% vs. 50 ± 5%; P < 0.01). Infarct size in the burn group was not significantly reduced. Irreversible ventricular fibrillation was 50% of all ventricular fibrillation in the burn group, while it was 25% in the sham group, however, this difference was not significant. Acute minor coetaneous burn has neither protective nor harmful for the rat myocardial ischemiareperfusion injury.

Recent studies have shown acute cardioprotective effects of cyclosporine. The aim of the present study was to determine the protective role of cyclosporine on the model simulated the rotational nodal arrhythmia (AVNRT) by using extracellular field potential recordings of isolated atrioventricular-node (AV-node) of rabbit. This study was performed on isolated double-perfused AV-node of male New Zealand rabbits (1.5-2.5 kg) in one group (n=7). Basic and rate-dependent stimulation protocols (recovery, facilitation, fatigue) and arrhythmia threshold (index of refractoriness) and % Gap incidence were measured for assessment of electrophysiological properties of the AV- node. All stimulation protocols were repeated in control step and in the presence of various cumulative concentrations of cyclosporine (0.5 - 10 μm). Cyclosporine prolonged the effective refractory period from 114.3±7.9 to 142±7.3 msec at the concentration of 10 μm. It also prolonged the functional refractory period from 162±3.3 to 178.6±5 msec and increased the time of Wenckebach at the concentrations of 5 - 10 μM. Various concentrations of cyclosporine increased fatigue and reached a significant level at 10 μm. Gap incidence was 82%, 16.6% and 20% in the control and treatments with 0.5 and 10 μm of cyclosporine, respectively. Block of MPTP by cyclosporine caused inhibition of basic and rate-dependent properties of atrioventricular node. Cyclosporine, by raising the threshold of arrhythmia, could be possibly considered as an anti- AVNRT drug.

β-carbolines (BCs) are heterocyclic indole alkaloids found in human body, grilled meat, alcoholic beverages and tobacco smoke. Based on the present reports, there are controversies about the role of these compounds in the pathophysiology of Parkinson' disease (PD). The aim of this study was to investigate the effect of norharman, a BC, in the prevention, exacerbation or creation of PD in 6-hydroxydopamine (6-OHDA) rat model. In the first part of this study, PD was established in rats by stereotaxic injection of 6-OHDA into the striatum. At the 2nd and 4th weeks post-surgery, apomorphine-induced rotational test was performed. Just before the surgery to the 4th week, after that rats received i.p. daily injections of norharman or its solvent at different doses. In the second part of the study, other groups of rats received daily intraperitoneal injections of norharman at different doses without prior injections of 6-OHDA. Fifteen and 30 days after the beginning of the injections, apomorphine-induced rotational and elevated body swing tests were performed. In the 6-OHDA-induced Parkinsonism rats, daily injection of norharman at doses of 200 and 1000, but not 100 μg/kg, significantly increased apomorphine-induced rotations compared to the control group at the 4th week postsurgery. In the intact rats, daily injection of norharman at doses of 200, 500 and 1000 μg/kg could not produce any PD symptoms in the apomorphine-induced rotational and elevated body swing tests. Longtime exposure to BCs can exacerbate PD but it cannot create the disease.

Previous studies have shown that sesame oil affects memory and learning. In the present work, effect of a diet containing 10% sesame oil used during pregnancy was evaluated on short-term passive avoidance learning of offspring rats by Shuttle box.

Female Wistar rats were divided into 2 groups (n = 9 each group). Control group consumed regular diet during pregnancy and the treatment group received a diet containing 10% sesame oil. Male and female offspring were examined on the 30th day of their ages.

Passive avoidance learning of offsprings that their mother received sesame oil during pregnancy was significantly increased in comparison to the control group.

The results show that consumption of a diet containing 10% sesamin oil during pregnancy significantly increases short -term passive avoidance learning of offspring.

Pain as a complex process in the CNS has been extensively studied by many researchers. It has been found that pain is controlled by certain pathways in the CNS, one of most important of which is the descending noradrenergic system. The pathway begins with Locus Coeruleus (LC) nucleus and ends in the spinal cord. In this study, formalin test was used as a chemical and tonic pain test to determine the role of LC in modulating pain in this pathway.

30 Sprague-Dawley rats with mean±SD weight of 280±30 g were divided into 6 groups (3 test and 3 control groups). In the test groups, 0.5 μL lidocaine was injected in the left LC (group 1), right LC (group 2) or both LC (group 3) to make local anesthesia. Half μL of normal saline was injected to controls (groups 4–6). After 15 min of injection, 50 μL of 2.5% of formalin was injected SQ to the left hind paw of rats and the level of nociception was recorded every 15 sec for one hour.

The induction of unilateral pain (right hind paw) in rats, can affect not only the contralateral but also the ipsilateral LC nucleus.

The left and right LC nuclei have significant role on unidirectional nociception in formalin test in rats. The ipsilateral LC, however, has a minor effect on nociception.

Nowadays Opioids are gaining acceptance for the management of moderate to severe and chronic pain. In addition, a number of studies have shown that plasma levels of β-endorphin (βEP) in exercise trained are higher than sedentary rats. In our study we assume that exercise training can reduce pain after withdrawal syndrome in morphine-dependent rats. Male Wistar rats (250±20 g, N=24) were addicted by morphine sulfate 0.4mg/ml (for 21 days) and animals were submitted to swimming training, five days a week for 8 weeks, in which First 60 minutes for 3 weeks and then 90 minutes in two weeks and at the end 120 min for 3weeks. At the end of each stage of exercise protocol naloxan hydrochloride (3mg/kg.ip) was injected. Tail-flick was used to assess the effect of training on nociceptive threshold. Data showed that swimming aerobic exercise significantly increased pain threshold in trained control and addicted rats (p<0.05) while pain responses did not significantly change in sedentary control and addicted rats. Our results indicate that swimming training has analgesic property in morphine withdrawal-induced hyperalgesia in rats. Therefore, it can be used for the treatment and/or management of painful conditions.