Effects of dopaminergic drugs in the dorsal hippocampus of rats in the MK801-induced anxiolytic-like behavior

2011 ◽  
Vol 26 (S2) ◽  
pp. 441-441
Author(s):  
M.R. Zarrindast ◽  
M. Nasehi ◽  
M. Pournaghshband

IntroductionExcitatory transmission through glutamate receptors constitutes the main mode of synaptic signaling in the brain regions that are critical for cognition such as learning and anxiety.ObjectivesThe possible involvement of dorsal hippocampal (intra-CA1) dopaminergic receptor mechanism on the anxiolytic-like response induced by NMDA receptor antagonist, MK801 has been investigated in the present study.MethodsThe male wistar rats were used and the elevated plus maze apparatus has been used to test parameters (%OAT, %OAE, locomotor activity, grooming, rereading and defection) of anxiety-like behaviors in the present study.ResultsThe data indicated that intra-CA1 administration of MK801 (2 μg/rat, intra-CA1) increased %OAT and %OAE but not other exploratory behaviors, indicating an anxiolytic-like response. Moreover, intra-CA1injection SCH23390 (0.25, 0.5 and 1 μg/rat) and sulpiride (0.25, 0.5 and 0.75 μg/rat) by itselves, 5 min before testing have no effect on exploratory behaviors. On the other hand, co-administration of ineffective dose of SCH23390 (0.5 μg/rat) with ineffective dose of MK801 (1 g/rat) increased %OAT but not other exploratory behaviors, suggestion anxiolytic-like behaviors. Furthermore, intra-CA1 administration of different doses of sulpiride (0.12, 0.5 and 0.75 μg/rat) 5 min before injection of effective dose of MK801 (2 μg/rat) decreased %OAT and %OAE but did not other exploratory behaviors induced by MK801.ConclusionThe results may indicate modulatory effect dopaminergic system of CA1 in the anxiolytic-like response induced by MK801.

2011 ◽  
Vol 26 (S2) ◽  
pp. 436-436
Author(s):  
M.R. Zarrindast ◽  
M. Nasehi ◽  
N. Heidari ◽  
A. Torkaman Boutorabi

IntroductionSome investigations showed that the glutamate receptors have critical role for cognition such as learning and anxiety in the brain.ObjectivesThe possible involvement of cholinergic system of dorsal hippocampus in the anxiolytic-like response induced by NMDA receptor antagonist, MK801 has been investigated in the present study.MethodsThe male wistar rats were used and the elevated plus maze apparatus has been used to test parameters (%OAT, %OAE, locomotor activity, grooming, rereading and defection) of anxiety-like behaviors.ResultsThe data indicated that intra-CA1 administration of MK801 (2 μg/rat) increased %OAT and %OAE but did not other exploratory behaviors, indicating an anxiolytic-like response. Moreover, intra-hippocampal injection of cholinergic receptor antagonists, mecamylamine (2 μg/rat) and scopolamine (4 μg/rat) by itselves, 5 min before testing increased %OAT and %OAE, but did not alter locomotor activity and other exploratory behaviors, suggesting anxiolytic-like behavior. On the other hand, intra-CA1 co-administration of ineffective doses of scopolamine (3 μg/rat), but not mecamylamine (1 μg/rat) with ineffective dose of MK801 (1 μg/rat) increased %OAT and %OAE.ConclusionThe data may indicate that the possible involvement of cholinergic system of CA1 on anxiolytic-like response induced by MK801.


2011 ◽  
Vol 26 (4) ◽  
pp. 555-563 ◽  
Author(s):  
Mohammad Reza Zarrindast ◽  
Arash Aghamohammadi-Sereshki ◽  
Ameneh Rezayof ◽  
Parvin Rostami

The objective of the present study was to investigate the possible role of the N-methyl-D-aspartate (NMDA) receptor system of the central amygdala (CeA) in the anxiogenic-like effect of nicotine. Male Wistar rats with cannulas aimed to the CeA were submitted to the elevated plus-maze (EPM). Intraperitoneal (i.p.) injections of nicotine (0.6 and 0.8 mg/kg) decreased percentage open arm time spent (%OAT) and percentage open arm entries (%OAE), but not locomotor activity, indicating an anxiogenic-like response. Bilateral intra-CeA microinjection of NMDA (0.005–0.1 μ g/rat) decreased %OAT, but not %OAE and locomotor activity. Moreover, intra-CeA microinjection of NMDA (0.05 μ g) with an ineffective dose of nicotine (0.4 mg/kg, i.p.) reduced %OAT and %OAE without effect on locomotor activity. On the other hand, intra-CeA microinjection of the NMDA receptor antagonist D-AP5 (0.05–0.5 μ g/rat) increased both %OAT and %OAE, showing an anxiolytic-like effect of the drug. Co-administration of the same doses of D-AP5 with nicotine (0.6 mg/kg, i.p.) increased %OAT and %OAE, but not locomotor activity. Intra-CeA microinjection of D-AP5 reversed the response induced by NMDA (0.1 μ g/rat) in the EPM. The results may support the possible involvement of glutamate transmission, through NMDA receptors of central amygdala in the anxiogenic-like effect of nicotine in the EPM task.


2021 ◽  
Vol 12 (3) ◽  
pp. 84-91
Author(s):  
Aminu Imam ◽  
◽  
Christianah Oyegbola ◽  
Maryam Busari ◽  
Rukayat Jaji-Sulaimon ◽  
...  

Organophosphates are irreversible cholinesterase (ChE) inhibitors with neurological consequences, and there is not yet an effective antidote. Here, we investigated the effects of Nigella sativa oil (NSO) on the ChE inhibition, neurobehavioural and histopathological changes following dichlorvos (DDVP) ingestions in rats. Thirty-two male Wistar rats were randomised into four groups, receiving 1 ml/kg of normal saline, 8.8 mg/kg of DDVP, 8.8 mg/kg of DDVP and 1 ml/kg of NSO, and 1 ml/kg of NSO only respectively, for 14 consecutive days. Locomotor, anxiety-like behaviours and spatial working memory were assessed on the 14th day, using open field (OF), Y-maze and modified elevated plus maze paradigms. The rats were euthanized on the 15th day and the brains excised; three brains were fixed for histopathology, and the other five prepared for biochemical analysis of acetyl cholinesterase (AChE). DDVP exposure caused significant reductions in frontal, amygdala and cerebella AChE activity, spontaneous alternations, line crossing and rearing frequencies and time in centre square, and caused increase in freezing period, transfer latency and necrotic-like cells. NSO intervention was able to reverse DDVP effects on AChE activities, explorative, locomotor, anxiety and spatial memory behaviours in co-exposed rats. It also preserved the histological integrity of the investigated brain regions. It can be concluded that NSO, may be potent against organophosphates induced neurotoxicity and their neurobehavioural consequences through the modulation of AChE activities.


2021 ◽  
Vol 19 (1) ◽  
pp. 47-53
Author(s):  
Ilia Yu. Tissen ◽  
Polina A. Chepik ◽  
Andrei A. Lebedev ◽  
Leila A. Magarramova ◽  
Eugenii R. Bychkov ◽  
...  

INTRODUCTION: Kisspeptins (KISS), a group of brain neuropeptides are involved in sexual behavior. KISS activate the hypothalamic neurons that synthesize gonadotropin releasing hormone. KISS was also detected in the limbic system. Earlier, we showed the activation of sexual motivation after the administration of kisspeptin-10 without increasing the level of testosterone in male rats, which suggests the extrahypothalamic effect of KISS. The aim of this work was to study the possibility of aquisition of conditioned place preference of kisspeptin-10, as well as to study the emotional and investigational behavior in rats after intranasal peptide administration. METHODS: Conditioned place preference test (CPP), open field test (OP) and elevated plus maze (EPM) were used in male Wistar rats. RESULTS: When studying CPP, animals spent 78.6 6.3% of the time in the chamber associated with the administration of KISS compared to control animals with administration of physiological saline (51.2% of the experiment time; p 0.05). After kisspeptin-10 administration locomotor activity was 2-fold increased (p 0.05), and the number of sniffings was 2-fold increased too (p 0.05). The parameters did not significantly differ in animals treated with kisspeptin or saline in PCL. CONCLUSION: Thus repeated intranasal administration of kisspeptin-10 induces the aquisition of CPP in rats. This suggests that kisspeptin-10 can cause activity in the reward system or the activation of brain regions associated with this system, which ultimately leads to the formation of an emotionally positive state.


2019 ◽  
Vol 33 (12) ◽  
pp. 1588-1599 ◽  
Author(s):  
Elysia Sokolenko ◽  
Matthew R Hudson ◽  
Jess Nithianantharajah ◽  
Nigel C Jones

Background: Abnormalities in neural oscillations that occur in the gamma frequency range (30–80 Hz) may underlie cognitive deficits in schizophrenia. Both cognitive impairments and gamma oscillatory disturbances can be induced in healthy people and rodents by administration of N-methyl-D-aspartate receptor (NMDAr) antagonists. Aims: We studied relationships between cognitive impairment and gamma abnormalities following NMDAr antagonism, and attempted to reverse deficits with the metabotropic glutamate receptor type 2/3 (mGluR2/3) agonist LY379268. Methods: C57/Bl6 mice were trained to perform the Trial-Unique Nonmatching to Location (TUNL) touchscreen test for working memory. They were then implanted with local field potential (LFP) recording electrodes in prefrontal cortex and dorsal hippocampus. Mice were administered either LY379268 (3 mg/kg) or vehicle followed by the NMDAr antagonist MK-801 (0.3 or 1 mg/kg) or vehicle prior to testing on the TUNL task, or recording LFPs during the presentation of an auditory stimulus. Results: MK-801 impaired working memory and increased perseveration, but these behaviours were not improved by LY379268 treatment. MK-81 increased the power of ongoing gamma and high gamma (130–180 Hz) oscillations in both brain regions and regional coherence between regions, and these signatures were augmented by LY379268. However, auditory-evoked gamma oscillation deficits caused by MK-801 were not affected by LY379268 pretreatment. Conclusions: NMDA receptor antagonism impairs working memory in mice, but this is not reversed by stimulation of mGluR2/3. Since elevations in ongoing gamma power and regional coherence caused by MK-801 were improved by LY379268, it appears unlikely that these specific oscillatory abnormalities underlie the working memory impairment caused by NMDAr antagonism.


2021 ◽  
Vol 22 (15) ◽  
pp. 8091
Author(s):  
Grace Jang ◽  
M. Bruce MacIver

Ketamine is a clinical anesthetic and antidepressant. Although ketamine is a known NMDA receptor antagonist, the mechanisms contributing to antidepression are unclear. This present study examined the loci and duration of ketamine’s actions, and the involvement of NMDA receptors. Local field potentials were recorded from the CA1 region of mouse hippocampal slices. Ketamine was tested at antidepressant and anesthetic concentrations. Effects of NMDA receptor antagonists APV and MK-801, GABA receptor antagonist bicuculline, and a potassium channel blocker TEA were also studied. Ketamine decreased population spike amplitudes during application, but a long-lasting increase in amplitudes was seen during washout. Bicuculline reversed the acute effects of ketamine, but the washout increase was not altered. This long-term increase was statistically significant, sustained for >2 h, and involved postsynaptic mechanisms. A similar effect was produced by MK-801, but was only partially evident with APV, demonstrating the importance of the NMDA receptor ion channel block. TEA also produced a lasting excitability increase, indicating a possible involvement of potassium channel block. This is this first report of a long-lasting increase in excitability following ketamine exposure. These results support a growing literature that increased GABA inhibition contributes to ketamine anesthesia, while increased excitatory transmission contributes to its antidepressant effects.


2019 ◽  
Author(s):  
Gabriela P. Silote ◽  
Sabrina F.S. de Oliveira ◽  
Deidiane E. Ribeiro ◽  
Mayara S. Machado ◽  
Roberto Andreatini ◽  
...  

AbstractKetamine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, presents rapid and sustained antidepressant effect in clinical and preclinical studies. Regarding ketamine effects on anxiety, there is a widespread discordance among pre-clinical studies. To address this issue, the present study reviewed the literature (electronic database MEDLINE) to summarize the profile of ketamine effects in animal tests of anxiety/fear. We found that ketamine anxiety/fear-related effects may depend on the anxiety paradigm, schedule of ketamine administration and tested species. Moreover, there was no report of ketamine effects in animal tests of fear related to panic disorder (PD). Based on that finding, we evaluated if treatment with ketamine and another NMDA antagonist, MK-801, would induce acute and sustained (24 hours later) anxiolytic and/or panicolytic-like effects in animals exposed to the elevated T-maze (ETM). The ETM evaluates, in the same animal, conflict-evoked and fear behaviors, which are related, respectively, to generalized anxiety disorder and PD. Male Wistar rats were systemically treated with racemic ketamine (10, 30 and 80 mg/kg) or MK-801 (0.05 and 0.1 mg/kg) and tested in the ETM in the same day or 24 hours after their administration. Ketamine did not affect the behavioral tasks performed in the ETM acutely or 24 h later. MK-801 impaired inhibitory avoidance in the ETM only at 45 min post-injection, suggesting a rapid but not sustained anxiolytic-like effect. Altogether our results suggest that ketamine might have mixed effects in anxiety tests while it does not affect panic-related behaviors.HighlightsKetamine induces mixed effects in animal anxiety testsFew studies investigated the individual effects of S-ketamine in anxiety/fear testsNone study evaluated the effects of R-Ketamine on anxiety/fear-related behaviorsSystemic ketamine does not affect panic-like behaviors in the elevated T-maze


Folia Medica ◽  
2021 ◽  
Vol 63 (3) ◽  
pp. 377-384
Author(s):  
Anita Mihaylova ◽  
Ilia Kostadinov ◽  
Nina Doncheva ◽  
Delian Delev ◽  
Hristina Zlatanova

Introduction: Parkinson&rsquo;s disease (PD) is &#1072; neurodegenerative disorder characterized mainly by its motor symptoms. The non-motor symptoms including pain are increasingly recognized in the last few decades. Existing evidence suggests that the dopaminergic neurotransmission has an essential role in pain control. Aim: The aim of the present study was to investigate the antinociceptive effect of dopaminergic drugs pramipexole and tolcapone against chemical and thermal stimuli in naive rats. Materials and methods: Male Wistar rats divided into 8 groups (n=8): saline; diclofenac 25 mg/kg body weight (bw) (positive control); pramipexole 0.5; 1 and 3 mg/kg bw; tolacapone 5; 15 and 30 mg/kg bw. Paw pressure and plantar tests were performed. Paw withdrawal pressure and latent time were measured. Statistical analysis was done by SPSS 19. Results: In the paw pressure test, pramipexole, in a dose of 1 and 3 mg/kg bw and tolcapone in a dose of 30 mg/kg bw, increased significantly the latency at 1, 2, and 3 hours compared to saline (p<0.05). In the plantar test, only the highest dose of pramipexole reached significance at 3 hours compared to the control rats (p<0.05). In contrast to pramipexole the three experimental groups with tolcapone markedly increased the latent time at 1 and 3 hours compared to saline (p<0.05). Conclusions: Pramipexole and tolcapone reduce mechanical and thermal nociception in na&iuml;ve rats by enhancing dopaminergic neurotransmission at both spinal and supraspinal levels. In addition, tolcapone stimulates noradrenergic mediation which may contribute to its antinociceptive effect.


Sign in / Sign up

Export Citation Format

Share Document