NMDA RECEPTORS ARE INVOLVED IN THE ANTIDEPRESSANT-LIKE EFFECTS OF CAPSAICIN FOLLOWING AMPHETAMINE WITHDRAWAL IN MALE MICE

Abstract—Amphetamine withdrawal (AW) is accompanied by diminished pleasure and depression which plays a key role in drug relapse and addictive behaviors. There is no effi- cient treatment for AW-induced depression and underpinning mechanisms were not well determined. Considering both transient receptor potential cation channel, subfamily V, member 1 (TRPV1) and N-Methyl-D-aspartate (NMDA) receptors contribute to pathophysiology of mood and addictive disorders, in this study, we investigated the role of TRPV1 and NMDA receptors in mediating depressive-like behaviors following AW in male mice. Results revealed that administration of capsaicin, TRPV1 agonist, (100 lg/mouse, i.c.v.) and MK-801, NMDA receptor antagonist (0.005 mg/kg, i.p.) reversed AW-induced depressive-like behaviors in forced swimming test (FST) and splash test with no effect on animals’ locomotion. Co-administration of sub-effective doses of MK-801 (0.001 mg/kg, i.p.) and capsaicin (10 lg/mouse, i.c.v) exerted antidepressant-like effects in behavioral tests. Capsazepine, TRPV1 antagonist, (100 lg/mouse, i.c.v) and NMDA, NMDA receptor agonist (7.5 mg/kg, i.p.) abolished the effects of capsaicin and MK801, respectively. None of aforementioned treatments had any effect on behavior of control animals. Collectively, our findings showed that activation of TRPV1 and blockade of NMDA receptors produced antidepressant-like effects in male mice following AW, and these receptors are involved in AW-induced depressive-like behaviors. Further, we found that rapid antidepressant-like effects of capsaicin in FST and splash test are partly mediated by NMDA receptors. � 2016 Published by Elsevier Ltd on behalf of IBRO

Experiencing neonatal maternal separation increased the seizure threshold in adult male mice: Involvement of the opioid system

Experiencing early-life stress has been considered as a potent risk factor for the development of many of brain disorders, including seizures. Intervening mechanisms through which neonatal maternal separation (MS) alters the seizure susceptibility in adulthood have not been well studied. In the current study, by applying 180 min of MS stress (PND 2–14), we determined the seizure susceptibility and considered the role of the opioid system. Maternal separation increased the seizure threshold, and administration of anticonvulsant/proconvulsant doses of morphine (1 and 30 mg/kg, respectively) reversed the impact of MS. Using tail flick and hot plate tests, we exposed animals to 30 min Restraint stress (RS) and found that MS decreased the pain threshold, suggesting the hyporesponsiveness of the opioid system. These results supported the abnormal seizure activity observed in the MS mice and suggested that abnormalities in the opioid system following MS alter seizure susceptibility in later life

Morphine modulates the effects of histamine H1 and H3 receptors on seizure susceptibility in pentylenetetrazole-induced seizure model of mice

Histamine regulates release of neurotransmitters such as dopamine, serotonin, gamma-aminobutyric acid (GABA), glutamate and also is involved in several functions in central nervous system (CNS). It has been shown that histamine participates in disorders like seizure. It has been well documented that morphine dose-dependently induces anti or proconvulsant effects. In the current study, we firstly showed that morphine (1 mg/kg) exerts anticonvulsant effects which significantly reversed by naltrexone administration. Secondly, we determined seizure threshold for H1 and H3 receptors agonists and antagonists in mouse model of pentylenetetrazole (PTZ)-induced clonic seizures. Our results showed that activation of H1 receptors by 2-(2-Pyridyl)-ethylamine exerts anticonvulsant properties while inhibition of H1 receptors by pyrilamine maleate induced proconvulsant effects. Furthermore, we showed that immepip dihydrobromide, a H3 receptor agonist, increased seizure susceptibility to PTZ whereas thioperamide, a H3 receptor antagonist increased seizure threshold. We also revealed that pretreatment with morphine potently reversed the effects of histaminergic system on seizure threshold suggesting the involvement of opioid system in alteration of seizure threshold by histaminergic drug

Involvement of D1 and D2 dopamine receptors in the antidepressant-like effects of selegiline in maternal separation model of mouse.

Mother-infant interactions are known to be associated with the psychological well-being of an individual in adulthood. It is well accepted that emotional stress in early life, such as maternal separation (MS), leads to alterations in the neurotransmission systems of various brain regions, especially the mesolimbic dopaminergic system, and subsequently can increase the risk for development of psychiatric disorders including depression in adulthood. Selegiline is an irreversible monoamine oxidase (MAO) type B inhibitor which increases striatal dopamine levels and exerts an antidepressant effect. In this study, 180min of MS stress was applied to mice at postnatal day (PND) 2-14 followed by behavioral tests for determining depressive-like behaviors, such as forced swimming test (FST), splash test and sucrose preference test (SPT) in adult mice (PND 50). The open field test (OFT) also was applied to validate FST results. We used SCH23390 (D1 antagonist) and sulpiride (D2 antagonist) in order to determine the role of D1 and D2 dopamine receptors in antidepressant-like effects of selegiline. Our results revealed that MS provoked depressive-like behaviors in adult male mice, and the administration of selegiline attenuated depressive-like behaviors in MS mice. Our findings showed that D1 dopamine receptors facilitate the positive effects of selegiline on the passive behavior in the FST. Furthermore, antidepressant effects of selegiline on hedonic difficulties are mediated via D2 receptor in the SPT. The results of the splash test revealed that both D1 and D2 receptors mediate the protective effect of selegiline against motivational and self-care problems. Based on our results, we conclude that both D1 and D2 dopamine receptors are involved in mediating the antidepressant-like effect of selegiline. We found that D1 receptors mediate an effect on despair behavior, D2 receptors mediate an effect on anhedonia, and both D1 and D2 receptors contribute to the protective effects of selegiline on motivational complications

Experiencing neonatal maternal separation increased pain sensitivity in adult male mice: Involvement of oxytocinergic system

Early-life stress adversely affects the development of the brain, and alters a variety of behaviors such as pain in later life. In present study, we investigated how early-life stress (maternal separation or MS) can affect the nociceptive response later in life. We particularly focused on the role of oxytocin (OT) in regulating nociception in previously exposed (MS during early postnatal development) mice that were subjected to acute stress (restraint stress or RS). Further, we evaluated whether such modulation of pain sensation in MS mice are regulated by shared mechanisms of the OTergic and opioidergic systems. To do this, we assessed the underlying systems mediating the nociceptive response by administrating different antagonists (for both opioid and OTergic systems) under the different experimental conditions (control vs MS, and control plus RS vs MS plus RS). Our results showed that MS increased pain sensitivity in both tail-flick and hot-plate tests while after administration of OT (1 μg/μl/mouse, i.c.v) pain threshold was increased. Atosiban, an OT antagonist (10 μg/μl/mouse, i.c.v) abolished the effects of OT. While acute RS increased the pain threshold in control (and not MS) mice, treating MS mice with OT normalized the pain response to RS. This latter effect was reversed by atosiban and/or naltrexone, an opioid antagonist (0.5 μg/μl/mouse, i.c.v) suggesting that OT enhances the effect of endogenous opioids. OTergic system is involved in mediating the nociception under acute stress in mice subjected to early-life stress and OTergic and opioidergic systems interact to modulate pain sensitivity in MS mic

Investigation of Growth and Mortality Parameters and Maturity length in Crab, Rhithropanopeus harrisii (Gould, 1841) in Gorgan Bay

This study was carried out to determine growth and mortality parameters of mud crab R. harrisii during a period of 12 months from May 2017 to April 2018 in northeast parts of Gorgan Bay-southeast Caspian Sea. A total of 307 crabs were collected using small beach scene and snail traps, including 120 females and 187 males. The total length of the male crab ranged from 7.01 to 18.36 mm with a mean of 13.07±0.16 mm, while that of females ranged between 5.56 and 8.92 mm with a mean of 11.02±0.02 mm. The largest mean value of observed lengths, which is 20.52±0.50 mm, was in November and the lowest was recorded in May with the value of 12.84 ± 0.81 mm. Based on von Bertalanffy growth model, L-infinity and K parameters were 23.5cm and 1.63 years-1 for females and 22 cm and 1.1 year-1 for males. Using carapace width, the parameter of Lm50 was 12mm. The index ofɸ -Munro was 2.97 and 2.95 for males and females respectively. The results on growth and reproduction of the species provided in this were the first one and could be useful in conservation plans of the species and Miankaleh wildlife refugee area as well

Some Parameters of Population dynamics of Palaemon adspersus (Rathke, 1837) in the South-east of the Caspian Sea (Gorgan Bay)

In this study, the population dynamics parameters of Baltic prawn, Palaemon adspersus were investigated in South-east Caspian Sea (Gorgan Bay). Specimens were collected monthly by using seine net (mesh size 5mm) between April 2016 and October 2016. Altogether, 434 prawns (163 females, 271 males) were captured. Maximum length, carapas length and weight were 76.20 mm, 18.27 mm and 5.621g for females and 62.69 mm, 14.06 mm and 2.306 g in males, respectively. Maximum length frequency was observed in total length range of 65-69 mm and 45-49 mm for females and males, respectively. Sex ratio for collected prawns was 62% for males and 38% for females. The von Bertalanffy growth equation was calculated as Lt=66.15[1-e-0/71(t+0.18)] for males, Lt=78.75[1-e-1/10(t+0.36)] for females and Lt=78.75[1-e-0/79(t+0.51)] for population. Growth performance (Φ') was higher (3.88) in females than that of males (3.49). Maximum calculated age was 4.05 and 2.37 years for males and females, respectively. The estimated value for total mortality (Z), natural mortality (M) and fishing mortality (F) were 3.74, 1.36 and 2.38 per year for females and 2.88, 1.08 and 1.80 per year for males, respectively. Exploitation rate (E) was calculated 0.63 and 0.64 for males and females, respectively

Association between Chronic Pain and Depression among the Elderly of Amirkola City, Northern Iran

Introduction: Chronic pain and depression are two of common geriatric disorders. The aim of this study was to investigate the association between chronic pain and depressive symptoms in older people in Amirkola.   Methods: This cross-sectional study is part of Amirkola Health and Aging Project. It is an ongoing cohort project which was being conducted from 2011 on all people aged 60 and above in Amirkola city in northern part of Iran. One thousand six hundred and four older people were included in the study. Data related to chronic pains and their locations were collected using questionnaire by inquiring the elderly while depressive symptoms were gathered based on Geriatric Depression Scale. Data were analyzed by chi-square test and logistic regression in SPSS.   Results: The prevalence of chronic pain, depressive symptoms, and co-occurrence of chronic pain and depressive symptoms among the elderly was respectively 84.4%, 43.5%, and 39.8%. The odds ratio of having chronic pain in depressed people was more than non-depressed people (OR = 2.88; 95% CI = 2.11-3.94). Prevalence of chronic pain in hands, wrists, elbows, shoulders, neck, hip joints, knees, ankles, legs, and back were noticeable in people with symptoms of depression compared to those without depressive symptoms. In regression model, severity of depressive symptoms (OR = 1.73 (1.23 - 2.45)), being female (OR = 2.40 (1.68 - 3.45)), increasing age (OR = 1.03 (1.01 - 1.05) and having chronic diseases (OR = 1.24 (1.13-1.35) were among the important variables that influenced chronic pain.   Conclusion: This study showed, especially in women, significant association between chronic pain and depressive symptoms. It is essential to take prophylactic and treatment measures suitable for their control and treatment. &nbsp