Fatemeh Khakpai - Academia.edu (original) (raw)

Papers by Fatemeh Khakpai

Research paper thumbnail of Additive anxiolytic-like effect of citicoline and ACPA in the non-acute restraint stress (NARS) and acute restraint stress (ARS) mice

Physiology & behavior, Mar 1, 2024

Research paper thumbnail of Synergistic effect between citalopram and muscimol upon induction of anxiolytic- and antidepressant-like effects in male mice: An isobologram analysis

IBRO neuroscience reports, Feb 1, 2024

Research paper thumbnail of Nano-Stevia reduces the liver injury caused by streptozotocin (STZ)-induced diabetes in rats by targeting PEPCK/GCK genes, INSR pathway and apoptosis

Journal of Diabetes & Metabolic Disorders

Research paper thumbnail of The modulatory effects of tyrosol and nano-tyrosol on anxiety-like behavior and emotional memory in streptozotocin-induced diabetic rats

NeuroReport/Neuroreport, Jul 10, 2024

Research paper thumbnail of Osteogenic differentiation of pre-conditioned bone marrow mesenchymal stem cells with Nisin on modified poly-L-lactic-acid nanofibers

Regenerative Therapy, Dec 1, 2022

Tissue engineering is an interdisciplinary expertise that involves the use of nanoscaffolds for r... more Tissue engineering is an interdisciplinary expertise that involves the use of nanoscaffolds for repairing, modifying, and removing tissue defects and formation of new tissues. Mesenchymal stem cells (MSCs) can differentiate into a variety of cell types, and they are attractive candidates for tissue engineering. In the current study, the electrospinning process was used for nanofiber preparation, based on a poly-Llactic-acid (PLLA) polymer. The surface was treated with O 2 plasma to enhance hydrophilicity, cell attachment, growth, and differentiation potential. The nanoscaffolds were preconditioned with lipopolysaccharide (LPS) to enhance induction of differentiation. The nanoscaffolds were categorized by contact angle measurements and scanning electron microscopy. The MTT assay was used to analyze the rate of growth and proliferation of cells. Osteogenic differentiation of cultured MSCs was evaluated on nanofibers using common osteogenic markers, such as alkaline phosphatase activity, calcium mineral deposition, quantitative real-time polymerase chain reaction, and immunocytochemical analysis. Based on the in vitro results, primed MSCs with LPS on the PLLA nanoscaffold significantly enhanced the proliferation and osteogenesis of MSCs. Also, the combination of LPS and electrospun nanofibers can provide a new and suitable matrix to support stem cells' differentiation for bone tissue engineering.

Research paper thumbnail of An interaction between basolateral amygdala orexinergic and endocannabinoid systems in inducing anti-nociception in the rat formalin test

Research paper thumbnail of Stevia and especially Nano-Stevia induced anti-diabetic, antidepressant, and analgesic effects in streptozotocin-induced diabetic rats

Research Square (Research Square), Jul 21, 2023

Background Type 2 diabetes mellitus is a metabolic illness with numerous psychological complicati... more Background Type 2 diabetes mellitus is a metabolic illness with numerous psychological complications such as depression, and pain sense. Stevia rebaudiana Bertoni (stevia) is well-recognized due to its sweet taste and bene cial activities in blood glucose modulation. This study aimed to examine the effects of Stevia and Nano-stevia on the modulation of depression and pain behaviors in male diabetic rats. Methods Type 2 diabetes mellitus was produced via a single intraperitoneal administration of streptozotocin (50 mg/kg). Depression and pain behaviors were assessed using the forced swim test (FST) and formalin test, respectively. Results The results showed that induction of diabetes leads to enhancement of blood glucose, immobility time in the FST, as well as the duration of exing and licking behaviors both in the early and late phases of the formalin in male diabetic rats. Hence, induction of diabetes in male rats caused hyperglycemia, depressant-like effect, and hyperalgesic response which were reversed by drug treatment. Moreover, intragastrically administration of Stevia (1 ml/kg) and Nano-stevia (1 ml/kg) reversed the hyperglycemia, depressant-like effect, and hyperalgesic response in male diabetic rats. Interestingly, Nano-stevia showed the highest signi cant effect rather than Stevia. Conclusions The results of this study proposed the bene cial effects of Stevia and especially Nano-stevia on inducing anti-diabetic effects, antidepressant-like response, as well as the analgesic effects in male diabetic rats.

Research paper thumbnail of Combined treatment of scopolamine and group III mGluR antagonist, CPPG, exerts antidepressant activity without affecting anxiety-related behaviors

Physiology & Behavior, Oct 1, 2020

Clinical trials have revealed that the muscarinic receptor antagonist scopolamine produces a fast... more Clinical trials have revealed that the muscarinic receptor antagonist scopolamine produces a fast and potent antidepressant response. However, the anticholinergic adverse effects and the risk of psychosis at higher doses limit the widespread clinical use of scopolamine. Combination therapy of scopolamine and other antidepressants in treating depression has been suggested. Our experimentswere designed to examine the effects of the combining ineffective doses of scopolamine and a group III metabotropic glutamate receptor (mGluR) antagonist, CPPG, on depression-and anxiety-related behaviors in male NMRI mice. The forced swim test (FST) and the elevated plus maze (EPM) were selected to evaluate depression-and anxiety-related behaviors, respectively. Intraperitoneal (i.p.) administration of scopolamine (0.01-0.5 mg/kg) exerted profound antidepressive and anxiogenic effects. Intracerebroventricular (i.c.v.) administration of CPPG (12.5-50 nmol/mouse) elicited significant antidepressive and anxiolytic effects. Moreover, the ineffective dose of CPPG (12.5 nmol/mouse) plus ineffective doses of scopolamine (0.01 or 0.05 mg/kg) showed antidepressant-like effect while these combinations had no effect anxiety-related behaviors. It should be noted that none of the compounds altered locomotor activity. Results identify the combined administration of scopolamine and CPPG as a possible hopeful target in the future treatment of the depressive disorder.

Research paper thumbnail of Harmaline potentiates morphine-induced antinociception via affecting the ventral hippocampal GABA-A receptors in mice

European Journal of Pharmacology, Feb 1, 2021

Morphine is one of the most effective medications for treatment of pain, but its side effects lim... more Morphine is one of the most effective medications for treatment of pain, but its side effects limit its use. Therefore, identification of new strategies that can enhance morphine-induced antinociception and/or reduce its side effects will help to develop therapeutic approaches for pain relief. Considering antinociceptive efficacy of harmaline and also highlighted the important role of GABA-A receptors in the pain perception, this research aimed to determine whether the ventral hippocampal (vHip) GABA-A receptors are involved in the possible harmaline-induced enhancement of morphine antinociception. To achieve this, vHip regions of adult male mice were bilaterally cannulated and pain sensitivity was measured in a tail-flick apparatus. Intraperitoneally administration of morphine (0, 2, 4 and 6 mg/kg) or harmaline (0, 1.25, 5 and 10 mg/kg) increased the percentage of maximal possible effect (%MPE) and induced antinociception. Interestingly, co-administration of sub-effective doses of harmaline (5 mg/kg) and morphine (2 mg/kg) induced antinociception. Intra-vHip microinjection of muscimol (0, 200 and 300 ng/mice), a GABA-A receptor agonist, enhanced the anti-nociceptive effects of harmaline (2.5 mg/kg)+morphine (2 mg/kg) combination. Microinjection of the same doses of muscimol into the vHip by itself did not alter tail-flick latency. Intra-vHip microinjection of bicuculline (100 ng/mouse), a GABA-A receptor antagonist, did not cause a significant change in MPE%. Bicuculline (60 and 100 ng/mouse, intra-vHip) was administered with the harmaline (5 mg/kg)+morphine (2 mg/kg), and inhibited the potentiating effect of harmaline on morphine response. These findings favor the notion that GABAergic mechanisms in the vHip facilitate harmaline-induced potentiation of morphine response in the tail-flick test in part through GABA-A receptors. These findings shall provide insights and strategies into the development of pain suppressing drugs.

Research paper thumbnail of Additive effect of histamine and muscimol upon induction of antinociceptive and antidepressant effects in mice

Behavioural Pharmacology, May 26, 2023

We investigated the effects of histamine and GABAA receptor agents on pain and depression-like be... more We investigated the effects of histamine and GABAA receptor agents on pain and depression-like behaviors and their interaction using a tail-flick test and the forced swimming test (FST) in male mice. Our data revealed that intraperitoneal administration of muscimol (0.12 and 0.25 mg/kg) increased the percentage of maximum possible effect (%MPE) and area under the curve (AUC) of %MPE, indicating an antinociceptive response. Intraperitoneal injection of bicuculline (0.5 and 1 mg/kg) decreased %MPE and AUC of %MPE, suggesting hyperalgesia. Moreover, muscimol by reducing the immobility time of the FST elicited an antidepressant-like response but bicuculline by enhancing the immobility time of the FST caused a depressant-like response. Intracerebroventricular (i.c.v.) microinjection of histamine (5 µg/mouse) enhanced %MPE and AUC of %MPE. i.c.v. infusion of histamine (2.5 and 5 µg/mouse) decreased immobility time in the FST. Co-administration of different doses of histamine along with a sub-threshold dose of muscimol potentiated antinociceptive and antidepressant-like responses produced by histamine. Cotreatment of different doses of histamine plus a noneffective dose of bicuculline reversed antinociception and antidepressant-like effects elicited by histamine. Cotreatment of histamine, muscimol, and bicuculline reversed antinociceptive and antidepressant-like behaviors induced by the drugs. The results demonstrated additive antinociceptive and antidepressant-like effects between histamine and muscimol in mice. In conclusion, our results indicated an interaction between the histaminergic and GABAergic systems in the modulation of pain and depression-like behaviors.

Research paper thumbnail of Effect of citicoline and transcranial direct current stimulation on depressive-like behaviors in mice & quot

Behavioural Brain Research, Jul 1, 2023

Research paper thumbnail of Enhanced anxiolytic and analgesic effectiveness or a better safety profile of morphine and tramadol combination in cholestatic and addicted mice

Neuroreport, Sep 14, 2022

Research paper thumbnail of Intra-gastrically administration of Stevia and particularly Nano-Stevia reversed the hyperglycemia, anxiety, and memory impairment in streptozotocin-induced diabetic rats

Physiology & Behavior

Type II diabetes mellitus is a group of metabolic disorders considered chronic hyperglycemia resu... more Type II diabetes mellitus is a group of metabolic disorders considered chronic hyperglycemia resulting from deficits in insulin secretion or insulin function. This disease usually links with various psychological problems such as anxiety and cognitive dysfunctions. Stevia (Stevia rebaudiana Bertoni) is a natural and healthy substitute sweetener for sugar and artificial sweeteners. It has become essential for human diets and food manufacturers. The aim of this research was to investigate the effects of Stevia and Nano-stevia on the regulation of anxiety and memory processes in male diabetic rats. The elevated plus-maze (EPM) test-retest procedure was used to assess anxiety and memory in male diabetic rats. The findings exhibited that induction of diabetes caused a distorted cellular arrangement in the liver tissue of male rats. On the other hand, intra-gastrically administration of Stevia (1 ml/kg) and nano-Stevia (1 ml/kg) indicated a normal appearance in the liver tissue of male diabetic rats. Moreover, induction of diabetes caused the augmentation of blood glucose, reduction in time spent in%open-arm time (%OAT) on the test day, and enhancement of%OAT on the retest day. Therefore, induction of diabetes in rats produced hyperglycemia, anxiogenic effect, and memory impairment and these responses were reversed by drug treatment. Furthermore, intra-gastrically application of Stevia (1 ml/kg) and nano-Stevia (1 ml/kg) reversed the hyperglycemia, anxiogenic effect, and memory impairment in male diabetic rats. Interestingly, Nano-Stevia exhibited the highest significant response rather than Stevia. In conclusion, the results of this research suggested the beneficial properties of Stevia and particularly Nano-Stevia on inducing anti-diabetic effects, anxiolytic behavior, as well as memory improvement in male diabetic rats.

Research paper thumbnail of The effect of CA1 dopaminergic system in harmaline-induced amnesia

Neuroscience, 2015

In the present study, the effects of bilateral injections of dopaminergic drugs into the hippocam... more In the present study, the effects of bilateral injections of dopaminergic drugs into the hippocampal CA1 regions (intra-CA1) on harmaline-induced amnesia were examined in male mice. A one-trial step-down passive avoidance task was used for the assessment of memory retention in adult male mice. Pre-training intra-peritoneal (i.p.) administration of harmaline (1 mg/kg) induced impairment of memory retention. Moreover, intra-CA1 administration of dopamine D1 receptor antagonist, SCH23390 (0.02 μg/mouse), dopamine D1 receptor agonist, SKF38393 (0.5 μg/mouse), dopamine D2 receptor antagonist, sulpiride (1 μg/mouse) and dopamine D2 receptor agonist, quinpirole (0.25 and 0.5 μg/mouse) suppressed the learning of a single-trial passive avoidance task. Also, pre-training intra-CA1 injection of subthreshold doses of SCH23390 (0.001 μg/mouse) or sulpiride (0.25 μg/mouse) with the administration of harmaline (1 mg/kg, i.p.) reversed impairment of memory formation. However, pre-training intra-CA1 injection of SKF38393 (0.1 μg/mouse) or quinpirole (0.1 μg/mouse) increased pre-training harmaline (0.25 and 0.5 mg/kg, i.p.)-induced retrieval impairment. Moreover, SKF Ca blocker (SKF) (0.01 μg/mouse) decrease the amnesia induced by harmaline (1 mg/kg), while co-administration of SKF (0.01 μg/mouse)/sulpiride (0.25 μg/mouse) or SCH23390 (0.001 μg/mouse)/sulpiride (0.25 μg/mouse) potentiate amnesia caused by harmaline. These findings implicate the involvement of CA1 dopaminergic mechanism in harmaline-induced impairment of memory acquisition.

Research paper thumbnail of A possible neuroprotective property of ethanol and/or NeuroAiD on the modulation of cognitive function

Neurotoxicology and Teratology, Nov 1, 2020

Cognitive impairments and poor performance on tasks needing behavioral flexibility are observable... more Cognitive impairments and poor performance on tasks needing behavioral flexibility are observable in chronic alcohol exposure. NeuroAid decreases cognitive deficits and improves functional outcomes by restoring neuronal circuits. The aim of the current study was to assess the hypothesis that ethanol exposure would induce neurobehavioral defects which may be reversed by the neuroprotective property of NeuroAid. Adult male Wistar rats were treated with saline, ethanol (0.2 g/kg), NeuroAid (0.8 g/kg) and ethanol (0.2 g/kg) + NeuroAid (0.8 g/kg). Then, behavioral tests were performed using the Y-maze apparatus, hot-plate and tail-flick apparatuses, locomotion apparatus as well as the loss of righting reflex (LORR) and hanging protocols (performance in a wire hanging test). Our results indicated that intraperitoneal (i.p.) administration of ethanol alone and administration of ethanol along with NeuroAid for one week reversed ethanol-induced spatial memory deficits in rats (P < 0.01). Interestingly, treatment with ethanol (0.2 g/kg) for one week induced nociception (P < 0.01). Moreover, one week administration of ethanol (0.2 g/kg) along with NeuroAid (0.8 g/kg) increased latency to LORR (P < 0.001) while four weeks administration of ethanol (0.2 g/kg) along with NeuroAid (0.8 g/kg) decreased sleep time (P < 0.01). In addition, a single administration of all drugs did not alter locomotor activity (P > 0.05) and hanging (P > 0.05). Improvement of behavioral tasks after one-week i.p. administration of ethanol and/or NeuroAid in comparison with a single administration of ethanol and/or NeuroAid may be due to the neuroprotective property of ethanol and/or NeuroAiD.

Research paper thumbnail of The effect of nicotine on antidepressant and anxiolytic responses induced by citalopram and citicoline in mice

Acta Neurobiologiae Experimentalis

The effect of nicotine on both anxiety and depression has been broadly studied. Moreover, citalop... more The effect of nicotine on both anxiety and depression has been broadly studied. Moreover, citalopram and citicoline play a role in the modulation of anxiety and depression. This study was designed to examine the effects of nicotine on the antidepressant and anxiolytic responses induced by citalopram and citicoline in mice. Anxiety‑ and depression‑related behaviors were assessed with the elevated plus maze and forced swim test, respectively. The results showed that subcutaneous administration of nicotine decreased open‑arm time (OAT) and open‑arm entries (OAE) but increased immobility time, suggesting anxiogenic‑like and depressive‑like effects. Intraperitoneal administration of citalopram increased OAT but decreased immobility time, indicating that citalopram induced anxiolytic‑like and antidepressant‑like responses. Additionally, an injection of citicoline increased OAE but decreased immobility time, revealing anxiolytic‑like and antidepressant‑like effects. Interestingly, the subt...

Research paper thumbnail of A synergistic analgesic effect of morphine in combination with the CB1 receptor agonist, ACPA, in normal, hypothyroid, and hyperthyroid male rats

Acta Neurobiologiae Experimentalis

Both cannabinoid and opioid receptors are involved in pain behavior. The administration of morphi... more Both cannabinoid and opioid receptors are involved in pain behavior. The administration of morphine and cannabis in rats has been shown to decrease thyroid weight and thyroid‑stimulating hormone (TSH) levels. We hypothesized that the third ventricle, due to its adjacency to the hypothalamus, is involved in the modulation of hypothalamic‑pituitary‑thyroid axis activity and descending pain pathways. The present study examined the effect of intra‑third ventricle administration of morphine and cannabis agents on the modulation of pain behavior in normal, hypothyroid (increased serum TSH), and hyperthyroid (decreased serum TSH) rats using the tail‑flick test. The results indicated that intra‑third ventricle injection of AM251 (CB1 receptor antagonist) caused hyperalgesia, while intra‑third ventricle administration of ACPA (CB1 receptor agonist) and morphine produced analgesia in normal, hypothyroid, and hyperthyroid rats. A non‑effective dose of morphine (0.5 μg/rat) did not attenuate hy...

Research paper thumbnail of Antinociceptive and antidepressive efficacies of the combined ineffective doses of S-ketamine and URB597

Naunyn-Schmiedeberg's Archives of Pharmacology

Research paper thumbnail of The effect of CA1 dopaminergic system on amnesia induced by harmane in mice

Research paper thumbnail of The dorsal hippocampal group III metabotropic glutamate receptors are involved in morphine effect on memory formation in male mice

European Journal of Pharmacology

Research paper thumbnail of Additive anxiolytic-like effect of citicoline and ACPA in the non-acute restraint stress (NARS) and acute restraint stress (ARS) mice

Physiology & behavior, Mar 1, 2024

Research paper thumbnail of Synergistic effect between citalopram and muscimol upon induction of anxiolytic- and antidepressant-like effects in male mice: An isobologram analysis

IBRO neuroscience reports, Feb 1, 2024

Research paper thumbnail of Nano-Stevia reduces the liver injury caused by streptozotocin (STZ)-induced diabetes in rats by targeting PEPCK/GCK genes, INSR pathway and apoptosis

Journal of Diabetes & Metabolic Disorders

Research paper thumbnail of The modulatory effects of tyrosol and nano-tyrosol on anxiety-like behavior and emotional memory in streptozotocin-induced diabetic rats

NeuroReport/Neuroreport, Jul 10, 2024

Research paper thumbnail of Osteogenic differentiation of pre-conditioned bone marrow mesenchymal stem cells with Nisin on modified poly-L-lactic-acid nanofibers

Regenerative Therapy, Dec 1, 2022

Tissue engineering is an interdisciplinary expertise that involves the use of nanoscaffolds for r... more Tissue engineering is an interdisciplinary expertise that involves the use of nanoscaffolds for repairing, modifying, and removing tissue defects and formation of new tissues. Mesenchymal stem cells (MSCs) can differentiate into a variety of cell types, and they are attractive candidates for tissue engineering. In the current study, the electrospinning process was used for nanofiber preparation, based on a poly-Llactic-acid (PLLA) polymer. The surface was treated with O 2 plasma to enhance hydrophilicity, cell attachment, growth, and differentiation potential. The nanoscaffolds were preconditioned with lipopolysaccharide (LPS) to enhance induction of differentiation. The nanoscaffolds were categorized by contact angle measurements and scanning electron microscopy. The MTT assay was used to analyze the rate of growth and proliferation of cells. Osteogenic differentiation of cultured MSCs was evaluated on nanofibers using common osteogenic markers, such as alkaline phosphatase activity, calcium mineral deposition, quantitative real-time polymerase chain reaction, and immunocytochemical analysis. Based on the in vitro results, primed MSCs with LPS on the PLLA nanoscaffold significantly enhanced the proliferation and osteogenesis of MSCs. Also, the combination of LPS and electrospun nanofibers can provide a new and suitable matrix to support stem cells' differentiation for bone tissue engineering.

Research paper thumbnail of An interaction between basolateral amygdala orexinergic and endocannabinoid systems in inducing anti-nociception in the rat formalin test

Research paper thumbnail of Stevia and especially Nano-Stevia induced anti-diabetic, antidepressant, and analgesic effects in streptozotocin-induced diabetic rats

Research Square (Research Square), Jul 21, 2023

Background Type 2 diabetes mellitus is a metabolic illness with numerous psychological complicati... more Background Type 2 diabetes mellitus is a metabolic illness with numerous psychological complications such as depression, and pain sense. Stevia rebaudiana Bertoni (stevia) is well-recognized due to its sweet taste and bene cial activities in blood glucose modulation. This study aimed to examine the effects of Stevia and Nano-stevia on the modulation of depression and pain behaviors in male diabetic rats. Methods Type 2 diabetes mellitus was produced via a single intraperitoneal administration of streptozotocin (50 mg/kg). Depression and pain behaviors were assessed using the forced swim test (FST) and formalin test, respectively. Results The results showed that induction of diabetes leads to enhancement of blood glucose, immobility time in the FST, as well as the duration of exing and licking behaviors both in the early and late phases of the formalin in male diabetic rats. Hence, induction of diabetes in male rats caused hyperglycemia, depressant-like effect, and hyperalgesic response which were reversed by drug treatment. Moreover, intragastrically administration of Stevia (1 ml/kg) and Nano-stevia (1 ml/kg) reversed the hyperglycemia, depressant-like effect, and hyperalgesic response in male diabetic rats. Interestingly, Nano-stevia showed the highest signi cant effect rather than Stevia. Conclusions The results of this study proposed the bene cial effects of Stevia and especially Nano-stevia on inducing anti-diabetic effects, antidepressant-like response, as well as the analgesic effects in male diabetic rats.

Research paper thumbnail of Combined treatment of scopolamine and group III mGluR antagonist, CPPG, exerts antidepressant activity without affecting anxiety-related behaviors

Physiology & Behavior, Oct 1, 2020

Clinical trials have revealed that the muscarinic receptor antagonist scopolamine produces a fast... more Clinical trials have revealed that the muscarinic receptor antagonist scopolamine produces a fast and potent antidepressant response. However, the anticholinergic adverse effects and the risk of psychosis at higher doses limit the widespread clinical use of scopolamine. Combination therapy of scopolamine and other antidepressants in treating depression has been suggested. Our experimentswere designed to examine the effects of the combining ineffective doses of scopolamine and a group III metabotropic glutamate receptor (mGluR) antagonist, CPPG, on depression-and anxiety-related behaviors in male NMRI mice. The forced swim test (FST) and the elevated plus maze (EPM) were selected to evaluate depression-and anxiety-related behaviors, respectively. Intraperitoneal (i.p.) administration of scopolamine (0.01-0.5 mg/kg) exerted profound antidepressive and anxiogenic effects. Intracerebroventricular (i.c.v.) administration of CPPG (12.5-50 nmol/mouse) elicited significant antidepressive and anxiolytic effects. Moreover, the ineffective dose of CPPG (12.5 nmol/mouse) plus ineffective doses of scopolamine (0.01 or 0.05 mg/kg) showed antidepressant-like effect while these combinations had no effect anxiety-related behaviors. It should be noted that none of the compounds altered locomotor activity. Results identify the combined administration of scopolamine and CPPG as a possible hopeful target in the future treatment of the depressive disorder.

Research paper thumbnail of Harmaline potentiates morphine-induced antinociception via affecting the ventral hippocampal GABA-A receptors in mice

European Journal of Pharmacology, Feb 1, 2021

Morphine is one of the most effective medications for treatment of pain, but its side effects lim... more Morphine is one of the most effective medications for treatment of pain, but its side effects limit its use. Therefore, identification of new strategies that can enhance morphine-induced antinociception and/or reduce its side effects will help to develop therapeutic approaches for pain relief. Considering antinociceptive efficacy of harmaline and also highlighted the important role of GABA-A receptors in the pain perception, this research aimed to determine whether the ventral hippocampal (vHip) GABA-A receptors are involved in the possible harmaline-induced enhancement of morphine antinociception. To achieve this, vHip regions of adult male mice were bilaterally cannulated and pain sensitivity was measured in a tail-flick apparatus. Intraperitoneally administration of morphine (0, 2, 4 and 6 mg/kg) or harmaline (0, 1.25, 5 and 10 mg/kg) increased the percentage of maximal possible effect (%MPE) and induced antinociception. Interestingly, co-administration of sub-effective doses of harmaline (5 mg/kg) and morphine (2 mg/kg) induced antinociception. Intra-vHip microinjection of muscimol (0, 200 and 300 ng/mice), a GABA-A receptor agonist, enhanced the anti-nociceptive effects of harmaline (2.5 mg/kg)+morphine (2 mg/kg) combination. Microinjection of the same doses of muscimol into the vHip by itself did not alter tail-flick latency. Intra-vHip microinjection of bicuculline (100 ng/mouse), a GABA-A receptor antagonist, did not cause a significant change in MPE%. Bicuculline (60 and 100 ng/mouse, intra-vHip) was administered with the harmaline (5 mg/kg)+morphine (2 mg/kg), and inhibited the potentiating effect of harmaline on morphine response. These findings favor the notion that GABAergic mechanisms in the vHip facilitate harmaline-induced potentiation of morphine response in the tail-flick test in part through GABA-A receptors. These findings shall provide insights and strategies into the development of pain suppressing drugs.

Research paper thumbnail of Additive effect of histamine and muscimol upon induction of antinociceptive and antidepressant effects in mice

Behavioural Pharmacology, May 26, 2023

We investigated the effects of histamine and GABAA receptor agents on pain and depression-like be... more We investigated the effects of histamine and GABAA receptor agents on pain and depression-like behaviors and their interaction using a tail-flick test and the forced swimming test (FST) in male mice. Our data revealed that intraperitoneal administration of muscimol (0.12 and 0.25 mg/kg) increased the percentage of maximum possible effect (%MPE) and area under the curve (AUC) of %MPE, indicating an antinociceptive response. Intraperitoneal injection of bicuculline (0.5 and 1 mg/kg) decreased %MPE and AUC of %MPE, suggesting hyperalgesia. Moreover, muscimol by reducing the immobility time of the FST elicited an antidepressant-like response but bicuculline by enhancing the immobility time of the FST caused a depressant-like response. Intracerebroventricular (i.c.v.) microinjection of histamine (5 µg/mouse) enhanced %MPE and AUC of %MPE. i.c.v. infusion of histamine (2.5 and 5 µg/mouse) decreased immobility time in the FST. Co-administration of different doses of histamine along with a sub-threshold dose of muscimol potentiated antinociceptive and antidepressant-like responses produced by histamine. Cotreatment of different doses of histamine plus a noneffective dose of bicuculline reversed antinociception and antidepressant-like effects elicited by histamine. Cotreatment of histamine, muscimol, and bicuculline reversed antinociceptive and antidepressant-like behaviors induced by the drugs. The results demonstrated additive antinociceptive and antidepressant-like effects between histamine and muscimol in mice. In conclusion, our results indicated an interaction between the histaminergic and GABAergic systems in the modulation of pain and depression-like behaviors.

Research paper thumbnail of Effect of citicoline and transcranial direct current stimulation on depressive-like behaviors in mice & quot

Behavioural Brain Research, Jul 1, 2023

Research paper thumbnail of Enhanced anxiolytic and analgesic effectiveness or a better safety profile of morphine and tramadol combination in cholestatic and addicted mice

Neuroreport, Sep 14, 2022

Research paper thumbnail of Intra-gastrically administration of Stevia and particularly Nano-Stevia reversed the hyperglycemia, anxiety, and memory impairment in streptozotocin-induced diabetic rats

Physiology & Behavior

Type II diabetes mellitus is a group of metabolic disorders considered chronic hyperglycemia resu... more Type II diabetes mellitus is a group of metabolic disorders considered chronic hyperglycemia resulting from deficits in insulin secretion or insulin function. This disease usually links with various psychological problems such as anxiety and cognitive dysfunctions. Stevia (Stevia rebaudiana Bertoni) is a natural and healthy substitute sweetener for sugar and artificial sweeteners. It has become essential for human diets and food manufacturers. The aim of this research was to investigate the effects of Stevia and Nano-stevia on the regulation of anxiety and memory processes in male diabetic rats. The elevated plus-maze (EPM) test-retest procedure was used to assess anxiety and memory in male diabetic rats. The findings exhibited that induction of diabetes caused a distorted cellular arrangement in the liver tissue of male rats. On the other hand, intra-gastrically administration of Stevia (1 ml/kg) and nano-Stevia (1 ml/kg) indicated a normal appearance in the liver tissue of male diabetic rats. Moreover, induction of diabetes caused the augmentation of blood glucose, reduction in time spent in%open-arm time (%OAT) on the test day, and enhancement of%OAT on the retest day. Therefore, induction of diabetes in rats produced hyperglycemia, anxiogenic effect, and memory impairment and these responses were reversed by drug treatment. Furthermore, intra-gastrically application of Stevia (1 ml/kg) and nano-Stevia (1 ml/kg) reversed the hyperglycemia, anxiogenic effect, and memory impairment in male diabetic rats. Interestingly, Nano-Stevia exhibited the highest significant response rather than Stevia. In conclusion, the results of this research suggested the beneficial properties of Stevia and particularly Nano-Stevia on inducing anti-diabetic effects, anxiolytic behavior, as well as memory improvement in male diabetic rats.

Research paper thumbnail of The effect of CA1 dopaminergic system in harmaline-induced amnesia

Neuroscience, 2015

In the present study, the effects of bilateral injections of dopaminergic drugs into the hippocam... more In the present study, the effects of bilateral injections of dopaminergic drugs into the hippocampal CA1 regions (intra-CA1) on harmaline-induced amnesia were examined in male mice. A one-trial step-down passive avoidance task was used for the assessment of memory retention in adult male mice. Pre-training intra-peritoneal (i.p.) administration of harmaline (1 mg/kg) induced impairment of memory retention. Moreover, intra-CA1 administration of dopamine D1 receptor antagonist, SCH23390 (0.02 μg/mouse), dopamine D1 receptor agonist, SKF38393 (0.5 μg/mouse), dopamine D2 receptor antagonist, sulpiride (1 μg/mouse) and dopamine D2 receptor agonist, quinpirole (0.25 and 0.5 μg/mouse) suppressed the learning of a single-trial passive avoidance task. Also, pre-training intra-CA1 injection of subthreshold doses of SCH23390 (0.001 μg/mouse) or sulpiride (0.25 μg/mouse) with the administration of harmaline (1 mg/kg, i.p.) reversed impairment of memory formation. However, pre-training intra-CA1 injection of SKF38393 (0.1 μg/mouse) or quinpirole (0.1 μg/mouse) increased pre-training harmaline (0.25 and 0.5 mg/kg, i.p.)-induced retrieval impairment. Moreover, SKF Ca blocker (SKF) (0.01 μg/mouse) decrease the amnesia induced by harmaline (1 mg/kg), while co-administration of SKF (0.01 μg/mouse)/sulpiride (0.25 μg/mouse) or SCH23390 (0.001 μg/mouse)/sulpiride (0.25 μg/mouse) potentiate amnesia caused by harmaline. These findings implicate the involvement of CA1 dopaminergic mechanism in harmaline-induced impairment of memory acquisition.

Research paper thumbnail of A possible neuroprotective property of ethanol and/or NeuroAiD on the modulation of cognitive function

Neurotoxicology and Teratology, Nov 1, 2020

Cognitive impairments and poor performance on tasks needing behavioral flexibility are observable... more Cognitive impairments and poor performance on tasks needing behavioral flexibility are observable in chronic alcohol exposure. NeuroAid decreases cognitive deficits and improves functional outcomes by restoring neuronal circuits. The aim of the current study was to assess the hypothesis that ethanol exposure would induce neurobehavioral defects which may be reversed by the neuroprotective property of NeuroAid. Adult male Wistar rats were treated with saline, ethanol (0.2 g/kg), NeuroAid (0.8 g/kg) and ethanol (0.2 g/kg) + NeuroAid (0.8 g/kg). Then, behavioral tests were performed using the Y-maze apparatus, hot-plate and tail-flick apparatuses, locomotion apparatus as well as the loss of righting reflex (LORR) and hanging protocols (performance in a wire hanging test). Our results indicated that intraperitoneal (i.p.) administration of ethanol alone and administration of ethanol along with NeuroAid for one week reversed ethanol-induced spatial memory deficits in rats (P < 0.01). Interestingly, treatment with ethanol (0.2 g/kg) for one week induced nociception (P < 0.01). Moreover, one week administration of ethanol (0.2 g/kg) along with NeuroAid (0.8 g/kg) increased latency to LORR (P < 0.001) while four weeks administration of ethanol (0.2 g/kg) along with NeuroAid (0.8 g/kg) decreased sleep time (P < 0.01). In addition, a single administration of all drugs did not alter locomotor activity (P > 0.05) and hanging (P > 0.05). Improvement of behavioral tasks after one-week i.p. administration of ethanol and/or NeuroAid in comparison with a single administration of ethanol and/or NeuroAid may be due to the neuroprotective property of ethanol and/or NeuroAiD.

Research paper thumbnail of The effect of nicotine on antidepressant and anxiolytic responses induced by citalopram and citicoline in mice

Acta Neurobiologiae Experimentalis

The effect of nicotine on both anxiety and depression has been broadly studied. Moreover, citalop... more The effect of nicotine on both anxiety and depression has been broadly studied. Moreover, citalopram and citicoline play a role in the modulation of anxiety and depression. This study was designed to examine the effects of nicotine on the antidepressant and anxiolytic responses induced by citalopram and citicoline in mice. Anxiety‑ and depression‑related behaviors were assessed with the elevated plus maze and forced swim test, respectively. The results showed that subcutaneous administration of nicotine decreased open‑arm time (OAT) and open‑arm entries (OAE) but increased immobility time, suggesting anxiogenic‑like and depressive‑like effects. Intraperitoneal administration of citalopram increased OAT but decreased immobility time, indicating that citalopram induced anxiolytic‑like and antidepressant‑like responses. Additionally, an injection of citicoline increased OAE but decreased immobility time, revealing anxiolytic‑like and antidepressant‑like effects. Interestingly, the subt...

Research paper thumbnail of A synergistic analgesic effect of morphine in combination with the CB1 receptor agonist, ACPA, in normal, hypothyroid, and hyperthyroid male rats

Acta Neurobiologiae Experimentalis

Both cannabinoid and opioid receptors are involved in pain behavior. The administration of morphi... more Both cannabinoid and opioid receptors are involved in pain behavior. The administration of morphine and cannabis in rats has been shown to decrease thyroid weight and thyroid‑stimulating hormone (TSH) levels. We hypothesized that the third ventricle, due to its adjacency to the hypothalamus, is involved in the modulation of hypothalamic‑pituitary‑thyroid axis activity and descending pain pathways. The present study examined the effect of intra‑third ventricle administration of morphine and cannabis agents on the modulation of pain behavior in normal, hypothyroid (increased serum TSH), and hyperthyroid (decreased serum TSH) rats using the tail‑flick test. The results indicated that intra‑third ventricle injection of AM251 (CB1 receptor antagonist) caused hyperalgesia, while intra‑third ventricle administration of ACPA (CB1 receptor agonist) and morphine produced analgesia in normal, hypothyroid, and hyperthyroid rats. A non‑effective dose of morphine (0.5 μg/rat) did not attenuate hy...

Research paper thumbnail of Antinociceptive and antidepressive efficacies of the combined ineffective doses of S-ketamine and URB597

Naunyn-Schmiedeberg's Archives of Pharmacology

Research paper thumbnail of The effect of CA1 dopaminergic system on amnesia induced by harmane in mice

Research paper thumbnail of The dorsal hippocampal group III metabotropic glutamate receptors are involved in morphine effect on memory formation in male mice

European Journal of Pharmacology