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

Protective effects of gabapentin against the seizure susceptibility and comorbid behavioral abnormalities in the early socially isolated mice

Adolescence is a pivotal period of brain development during lifespan, which is sensitive to stress exposure. Early social isolation stress (SIS) is known to provoke a variety of psychiatric comorbidities as well as seizure risk. Psychiatric comorbidities present challenging dilemmas for treatment and management in people with seizure disorders. In this study, we aimed to investigate whether gabapentin (GBP) as an anti-epileptic drug is able to alleviate the seizure activity as well as comorbid behavioral abnormalities in socially isolated mice. Results showed that early SIS induced proconvulsant effects along with depressive, aggressive and anxiety-like behaviors. Whereas the administration of both acute and chronic GBP at sub-effective doses produced no alterations in the behavioral profile of socially conditioned counterparts the same treatments effectively reversed the seizure susceptibility to pentylenetetrazole and behavioral deficits in isolated mice. Results of the study indicate that 1) Early SIS could be considered as an animal model of psychosocial stress to investigate the psychiatric comorbidities in seizure disorders, 2) Chronic administration of low dose GBP prevented the shaping of behavioral abnormalities in adulthood, 3) Chronic administration of low dose GBP produced no negative behavioral effects in socially conditioned mice suggesting the safety of the drug, 4) Gabapentin at low doses may be considered as an agent for management of epilepsy in individuals with psychiatric comorbidities

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

Interaction between dorso-hyppocampal histaminergic and medio-septal opioidergic systems in anxiety behavior

Septohippocampal system plays an important role in regulating fear and anxiety behaviors. In this study, the effects of histamine injected into the dorsal hippocampus and opioidergic agents into medial septum on the anxiety-like behaviors in rats were analyzed, using the Elevated Plus-Maze (EPM) test. Injection of 1 and 5 μg/rat histamine into dorsal hippocampus had no effect on anxiety-like behavior, while injection of 10 μg/rat histamine increased the percentage of open arm time (%OAT) and open arm entry (%OAE), which indicated the anxiolytic effects of histamine. Microinjection of morphine, μ-opioid receptor agonist, into the medial septum (1μg/rat) increased the (%OAT) and (%OAE). Doses of 0.25, 0.5 μg/rat morphine had no effect on anxiety. Co-administration of histamine ineffective dose (1μg/rat) to the dorsal hippocampus and ineffective dose of morphine (0.25µg/rat) to the medial septum increased the (%OAT) and (%OAE). Subsequently, injection of different doses of naloxone (1, 2, 4 µg/rat), as an opioid receptor antagonist, into the medial septum in the presence and absence of an effective dose of histamine (10 µg/rat) in the dorsal hippocampus, was studied. Injection of naloxone (4 µg/rat) into medial septum decreased the (%OAT) and (%OAE), but did not alter the locomotor activity, which indicated the anxiogenic effects of naloxone. Simultaneous injection of histamine (10 µg/rat) into dorsal hippocampus with doses of naloxone (1, 2, 4 µg/rat) into the medial septum, indicate anxiolytic effects and increased %OAT and %OAE in Elevated Plus Maze, although when the dose of naloxone was 4μg/rat, this effect was less observed. The results indicate that hippocampus histaminergic system interact with medial septum opioidergic system and the interaction of these systems modulates anxiety behavior

Impact of the interaction between morphine and α-noradrenergic system of basolateral Amygdala on anxiety-related behavior and memory

Basolateral Amygdala is an important site of anxiety. Interactions between α-adrenergic and opioidergic systems in Basolateral amygdale were used for investigation anxiety and memory. The elevated plus-maze has been employed. The male wistar rats were used for this test. The site of BLA was cannulated bilaterally. Rats we injected morphine (4, 5.6 mg/kg) intraperitonealy, while clonidine (1, 2, 4 µg/rat) and yohimbin (0.5, 1,2 µg/rat) were injected to BLA. Open arm time percentage (%OAT), open arm entry (%0AE) and locomotor activity were determined by this behavioral test. Retention tested 24 hours later. Administration of morphine (6mg/kg) increased the OAT% in anxiety test, indicating anxiolytic-like effect. Intra Basolateral amygdala infusion of clonidine (4μg/rat) has an anxiolytic-like effect. While co-administration clonidine (4μg/rat) and in effective dose of morphine (4mg/kg) showed significant increase of OAT% in anxiety test; thus presenting anxiolytic response. Intra Basolateral amygdala administration of yohimbine (2μg/rat) decreased OAT% indicating of decrease anxiety-like behavior. While co-administration of intra Basolateral amygdala clonidine (4μg/rat) and effective dose of morphine (6mg/kg) showed a significant increase of OAT%, presenting anxiolytic response; co-administration of ineffective doses of morphine (4mg/kg) and yohimbine (1μg/rat) with the effective dose of clonidine (4μg/rat) showed that yohimbine could reverse the anxiolytic-like effect of morphine and clonidine. It should be noted that there are no significant changes in locomotor activity. The results indicate that morphine creates the compromise changes in adrenergic neurons of Basolateral amygdala by changing the α-adrenergic system on anxiety

The role of cannabinoid system in consolidation of passive avoidance memory in the shell of nucleus accumbens in male Wistar rats

There are multiple neurotransmitters and neuromodulator systems mediating memory formation among which the endocannabinoid system plays a critical role in the memory formation by modulating the release of many neurotransmitters. Nucleus accumbens appears to have a site in the central of neuronal circuits of the limbic system and to be responsible for the integration and consolidation of inputs from other parts of the brain. In this study the influence of bilateral intra-nucleus accumbens shell microinjections of cannabinoid receptor agents on memory consolidation in adult male rats using passive avoidance task was investigated. The results showed that the intra-accumbens shell microinjection of ACPA as a CB1 receptor agonist (6 ng/rat) immediately after training decreased passive avoidance memory consolidation, while administration of its antagonist (AM251) at different doses did not affect passive avoidance memory consolidation. However, co-administration of AM251 (60 ng/rat) with an effective dose of ACPA prevented the impairment memory consolidation induced by ACPA. These results suggest that the accumbens shell cannabinoid system as a modulating system is involved in aversive memory consolidation including passive avoidance memory

Bupropion induces sniffing: a possible dopaminergic mechanism

The effect of bupropion, an antidepressant drug, on sniffing behaviour was examined in rats. Animals treated intraperitoneally (i.p.) with different doses of bupropion (5-40 mg/kg) showed sniffing behaviour in a dose-related manner. Pretreatment of animals (i.p.) with the dopamine antagonists SCH 23390 (0.025-0.1 mg/kg) or sulpiride (12.5-50 mg/kg) decreased the sniffing induced by bupropion. Reserpine pretreatment (2.5 mg/kg, i.p., 18 h) alone and in combination with o~-methyl-p-tyrosine (AMPT; 250 mg/kg, i.p.) also reduced the behaviour produced by the drug. The et-adrenoceptor phenoxybenzamine (5 and 10 mg/kg, i.p.) and the [3-adrenoceptor antagonist propranolol (5 and 10 mg/kg, i.p.) administered 60 rain prior to bupropion did not affect the drug's effect on sniffing. Propranolol alone, however, induced sniffing. The antimuscarinic atropine (5 and 10 mg/kg, i.p.) administered 30 min prior to bupropion increased the bupropion response. Atropine alone induced vigorous sniffing. It is concluded that bupropion induced sniffing through a dopaminergic mechanis

Efficiency of Information Coding in Various L/M Retinal Cone Ratios

Previous evidence has shown that the number of L and M cones in retina varies significantly between subjects. However, it is not clear how the variation of L/M ratio changes the behavioral performance of the subject. A model of transformation of data from retina to visual cortex for evaluation of various L/M cones ratios is presented. While L/M cone ratios close to 1 brings the best performance for one of postreceptoral (magnocellular) channels, we showed that the performance in the second channel (parvocells) will improve when the ratio furthers away from 1. Effects of different ratios of S were also explored

Anti-mitogenic and apoptotic effects of 5-HT1B receptor antagonist on HT29 colorectal cancer cell line

Purpose: There is lack of evidence about impact of 5-HT receptors on colorectal cancers. The current study was designed to investigate the role of serotonin and its receptors in colorectal cancer cell line and tissues. Methods: In cell cultures, we investigated the effects of 5-HT and 5-HT agonists and antagonists on proliferation of HT29 cells. We also tested apoptosis for the receptor antagonists. The expression of 5-HT1 receptor subtypes was examined by immunohistochemistry and western blotting. Results: Our data indicated that 5-HT receptor was fully expressed in HT29 cell line and tumor tissues. MTT proliferation assay also revealed that serotonin and CP93129 dihydrochloride, a selective 5-HT receptor agonist, stimulated growth of HT29 cells. Further, SB224289 hydrochloride (that is a selective 5-HT receptor antagonist) had anti-proliferative and apoptotic effects on HT29 cells. Conclusions: The findings of this study provide evidence for the potential role of 5-HT receptor in colorectal cancer. Further investigation is required to explore the effect of receptor antagonists on the prevention, prognosis and treatment of patients with colorectal cancer