Blockade of prelimbic glutamate receptor reduces the reinforcing effect of morphine

2018 ◽  
Vol 96 (8) ◽  
pp. 815-822 ◽  
Author(s):  
Fateme Aboutalebi ◽  
Hojjatallah Alaei ◽  
Shahrbanoo Oryan ◽  
Maryam Radahmadi
Keyword(s):  
Ampa Receptors ◽  
Nmda Antagonist ◽  
Saline Group ◽  
Glutamatergic Transmission ◽  
Self Administration ◽  
Morphine Group ◽  
Active Lever ◽  
Male Wistar Rats ◽  
Lever Pressing ◽  
Different Doses

The prelimbic cortex (PrL) as a part of the medial prefrontal cortex (mPFC) plays a crucial role in drug addiction. Previous studies have shown that glutamatergic transmission through the NMDA and AMPA receptors plays an important role in morphine rewarding properties. In this study, we evaluated the effect of glutamate receptors blockade within the PrL on morphine self-administration. Male Wistar rats were randomly selected and divided into 7 groups. Trained rats were placed in self-administration apparatus, where they pressed an active lever for receiving morphine (5 mg/mL) in test groups and saline in saline group during 11 consecutive days for 2 h per session. The effects of intra-prelimbic AMPA receptor antagonist (CNQX; 0.5 and 2.5 μg/0.5 μL) and the NMDA antagonist (AP5; 0.1 and 1 μg/0.5 μL) on self-administration were tested. Our results demonstrated that intra-prelimbic injection of different doses of CNQX and AP5, and co-administration of these 2 drugs before self-administration significantly decreased active lever pressing compared with morphine group (p < 0.001). Also, the number of self-infusion significantly decreased in test groups compared with morphine group (p < 0.001). These findings suggest that a reduction in PrL glutamatergic output can modulate morphine reinforcement.

scholarly journals The blockade of D1/D2-like dopamine receptors in the lateral periaqueductal gray region affects morphine self-administration with and without exercise in rats

2020 ◽  
Vol 25 (1) ◽  
pp. 57-68
Author(s):  
Somayeh Ahmadi ◽  
◽  
Maryam Radahmadi ◽  
Safoura Alizadeh ◽  
Hojatallah Alaei ◽  
...  
Keyword(s):  
Exercise Training ◽  
Dopamine Receptors ◽  
Dopaminergic System ◽  
Periaqueductal Gray ◽  
Self Administration ◽  
Morphine Group ◽  
Reward Circuitry ◽  
Active Lever ◽  
Lever Pressing ◽  
To Receive

Introduction: The periaqueductal gray (PAG) region plays an essential role in the modulation of nociception. Also, lateral PAG (lPAG) is involved in reward circuitry by the dopaminergic system in addiction. The present study investigated the blockade of D1/D2-like dopamine receptors in the lateral PAG region affects morphine self-administration with and without exercise. Methods: Rats were divided into six groups. The rats were initially trained to receive small pellets of food by pressing an active lever in the self administration apparatus. Exercise groups were run on a treadmill at 20m/min, 5 days/week, for 4 weeks before the surgery. Then rats were bilaterally implanted with cannulae in lPAG. The SCH23390 and sulpiride were microinjected into the lPAG, 5min before receiving morphine. Afterward, the animals were allowed to self administer morphine in 2h sessions over 11 consecutive days. At last, the numbers of lever pressing, infusion times and withdrawal symptoms were measured. Results: The results showed the number of active lever pressing was significantly increased in the morphine group compared to other groups in self-infusion during 11 days. Exercise significantly reversed the detrimental effects of morphine self-administration after five days. However, the synergistic effect of injected sulpiride into the lPAG region with exercise training was more pronounced on the amelioration of morphine than on the combinatory effect of SCH23390 with exercise. Conclusion: The findings suggested that the D2 dopamine receptor in the lPAG region was involved in the morphine addiction via the dopaminergic system and exercise training in combination with antagonists could reduce the rewarding properties of morphine.

the Effects of Locus Coeruleus Inactivation on i.v Self Administration of Morphine and Morphine Withdrawal Symptoms in Rats

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
A. Alijarahi
Keyword(s):  
Locus Coeruleus ◽  
Infusion Pump ◽  
Test Session ◽  
Morphine Withdrawal ◽  
Male Rats ◽  
Opiate Withdrawal ◽  
Self Administration ◽  
Morphine Group ◽  
Lever Pressing ◽  
The Right

Biochemical, behavioral, and electrophysiologic studies indicate that activation of the noradrenergic cells in the Locus coeruleus (LC) play an important role in the symptoms of opiate withdrawal. There for in this study the effects of LC inactivation on self-administration of Morphine and on morphine withdrawal syndrome in rats has been investigated.Male rats (250-300gr) were anaesthetized and implanted with silastic catheters inserted in to the right jugular vein. after 5 days animals were fitted and the external end of the catheter was connected with a syringe-driven pump, then were placed in the self-administration apparatus that had two lever (active, passive) for 2 h every day. Active lever switched on the infusion pump for 10 sec, injecting. 1ml of saline or saline containing 5 mg/ml of morphine (training period was 10days). LC was inactivated by (1ul) lidocaein (%2) five min befor training.Animals were allowed to self administer morphine (1mg/kg per inf.) ten consecutive daily 2-h session. During all morphine self administration session lever pressing behavior was measured. Our results show that LC inactivation 5min before morphine self administration produced a significant decrease in the initiation of morphine self administration during all session. after the last test session morphine withdrawal symptom signs (MWS) precipitated by naloxone were measured. Our results show that most of MWS (but not all) were decreased by LC inactivation in comparison with morphine group.

scholarly journals Cannabinoid-Induced Conditioned Place Preference, Intravenous Self-Administration, and Behavioral Stimulation Influenced by Ghrelin Receptor Antagonism in Rats

2021 ◽  
Vol 22 (5) ◽  
pp. 2397
Author(s):  
Chrysostomos Charalambous ◽  
Tereza Havlickova ◽  
Marek Lapka ◽  
Nina Puskina ◽  
Romana Šlamberová ◽  
...  
Keyword(s):  
Conditioned Place Preference ◽  
Fixed Ratio ◽  
Place Preference ◽  
Self Administration ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Ghrelin Receptor ◽  
Addiction Therapy ◽  
Significant Efficacy ◽  
Lever Pressing

Cannabis/cannabinoids are widely used for recreational and therapy purposes, but their risks are largely disregarded. However, cannabinoid-associated use disorders and dependence are alarmingly increasing and an effective treatment is lacking. Recently, the growth hormone secretagogue receptor (GHSR1A) antagonism was proposed as a promising mechanism for drug addiction therapy. However, the role of GHS-R1A and its endogenous ligand ghrelin in cannabinoid abuse remains unclear. Therefore, the aim of our study was to investigate whether the GHS-R1A antagonist JMV2959 could reduce the tetrahydrocannabinol (THC)-induced conditioned place preference (CPP) and behavioral stimulation, the WIN55,212-2 intravenous self-administration (IVSA), and the tendency to relapse. Following an ongoing WIN55,212-2 self-administration, JMV2959 3 mg/kg was administered intraperitoneally 20 min before three consequent daily 120-min IVSA sessions under a fixed ratio FR1, which significantly reduced the number of the active lever-pressing, the number of infusions, and the cannabinoid intake. Pretreatment with JMV2959 suggested reduction of the WIN55,212-2-seeking/relapse-like behavior tested in rats on the twelfth day of the forced abstinence period. On the contrary, pretreatment with ghrelin significantly increased the cannabinoid IVSA as well as enhanced the relapse-like behavior. Co-administration of ghrelin with JMV2959 abolished/reduced the significant efficacy of the GHS-R1A antagonist in the cannabinoid IVSA. Pretreatment with JMV2959 significantly and dose-dependently reduced the manifestation of THC-induced CPP. The THC-CPP development was reduced after the simultaneous administration of JMV2959 with THC during conditioning. JMV2959 also significantly reduced the THC-induced behavioral stimulation in the LABORAS cage. Our findings suggest that GHS-R1A importantly participates in the rewarding/reinforcing effects of cannabinoids.

Histopathological changes in the liver and kidney tissues of Wistar albino rat exposed to fenitrothion

2008 ◽  
Vol 24 (9) ◽  
pp. 581-586 ◽  
Author(s):  
S Afshar ◽  
AA Farshid ◽  
R Heidari ◽  
M Ilkhanipour
Keyword(s):  
Control Group ◽  
Histopathological Changes ◽  
Albino Rat ◽  
Hydropic Degeneration ◽  
Leukocytic Infiltration ◽  
Male Wistar Rats ◽  
Liver And Kidney ◽  
Dose Dependent ◽  
Significant Injury ◽  
Different Doses

The aim of this study was to investigate the dose-related effects of fenitrothion (FNT) on the liver and kidney. The study was conducted on 8-week-old male Wistar rats that were divided into four groups (three experimental groups and one control group) and were treated orally with different doses (25, 50, 100 mg/kg) of FNT for 28 consecutive days. After treatment, the rats were anesthetized with ether and liver and kidney samples were taken for histological studies. The results showed that the histopathological changes in the liver were mainly represented by parenchymatous degeneration of hepatocytes with mild necrosis, leukocytic infiltration in the portal area, severe congestion, and hemorrhage. These changes were dose dependent. Marked tubular dilation, hydropic degeneration in tubular epithelium, moderate congestion, and hemorrhage in the cortical and medulla part of the kidney were recorded. Histopathologic examination of the liver and kidney indicated a significant injury only in rats receiving 100 mg/kg FNT.

Genotoxic and mutagenic effects of vigabatrin, a γ-aminobutyric acid transaminase inhibitor, in Wistar rats submitted to rotarod task

2016 ◽  
Vol 35 (9) ◽  
pp. 958-965 ◽  
Author(s):  
VR Coelho ◽  
K Sousa ◽  
TR Pires ◽  
DKM Papke ◽  
CG Vieira ◽  
...  
Keyword(s):  
Acute Treatment ◽  
Wistar Rats ◽  
Micronucleus Test ◽  
Repeated Administration ◽  
Saline Group ◽  
Aminobutyric Acid ◽  
Subchronic Treatment ◽  
Motor Activities ◽  
Male Wistar Rats ◽  
Mutagenic Effects

Vigabatrin (VGB) is an antiepileptic drug thatincreases brain γ-aminobutyric acid (GABA) levels through irreversible inhibition of GABA transaminase. The aim of this study was to evaluate neurotoxicological effects of VGB measuring motor activity and genotoxic and mutagenic effects after a single and repeated administration. Male Wistar rats received saline, VGB 50, 100, or 250 mg/kg by gavage for acute and subchronic (14 days) treatments and evaluated in the rotarod task. Genotoxicity was evaluated using the alkaline version of the comet assay in samples of blood, liver, hippocampus, and brain cortex after both treatments. Mutagenicity was evaluated using the micronucleus test in bone marrow of the same animals that received subchronic treatment. The groups treated with VGB showed similar performance in rotarod compared with the saline group. Regarding the acute treatment, it was observed that only higher VGB doses induced DNA damage in blood and hippocampus. After the subchronic treatment, VGB did not show genotoxic or mutagenic effects. In brief, VGB did not impair motor activities in rats after acute and subchronic treatments. It showed a repairable genotoxic potential in the central nervous system since genotoxicity was observed in the acute treatment group.

scholarly journals Influence of preoperative supplementation of omega-3 fatty acid in the healing of colonic anastomoses in malnourished rats receiving paclitaxel

2015 ◽  
Vol 42 (2) ◽  
pp. 116-123 ◽  
Author(s):  
Alvo Orlando Vizzotto Junior ◽  
Antonio Carlos Ligocki Campos ◽  
Eneri Vieira de Souza Leite Mello ◽  
Tiago Jacometo Castilho
Keyword(s):  
Fatty Acids ◽  
Rupture Strength ◽  
Saline Group ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Colonic Anastomoses ◽  
Omega 3 Fatty Acid ◽  
Paclitaxel Group ◽  
Male Wistar Rats ◽  
Maturation Index

OBJECTIVE: To evaluate the effect of preoperative supplementation of omega-3 fatty acids on the healing of colonic anastomoses in malnourished rats receiving paclitaxel. METHODS: we studied 160 male Wistar rats, divided in two groups: one subjected to malnutrition by pair feeding (M) for four weeks, and another that received food ad libitum (W). In the fourth week, the groups were further divided into two subgroups that received omega-3 or olive oil by gavage. The animals were submitted to colonic transection and end-to-end anastomosis. After the operation, each of the four groups was divided into two subgroups that received intraperitoneal isovolumetric solutions of saline or paclitaxel. RESULTS: mortality was 26.8% higher in the group of animals that received paclitaxel (p = 0.003). The complete rupture strength was greater in well-nourished-oil Paclitaxel group (WOP) compared with the the malnourished-oil Paclitaxel one (MOP). The collagen maturation index was higher in well-nourished-oil saline group (WOS) in relation to the malnutrition-oil-saline group (MOS), lower in malnourished-oil-saline group (MOS) in relation to malnourished-ômega3-saline one (M3S) and lower in the well-nourished-omega3-saline group (W3S) compared with the malnourished-omega3-saline (M3S). The blood vessel count was higher in the malnourished-oil-saline group (MOS) than in the malnourished-oil-paclitaxel group (MOP) and lower in the malnourished-oil-saline group (MOS) in relation to the malnourished-omega3-paclitaxel group (M3P). CONCLUSION: supplementation with omega-3 fatty acids was associated with a significant increase in the production of mature collagen in malnourished animals, with a reversal of the harmful effects caused by malnutrition associated with the use of paclitaxel on the rupture strength, and with a stimulus to neoangiogenesis in the group receiving paclitaxel.

scholarly journals Ketamine effects on anxiety and fear-related behaviors: current literature evidence and new findings

2019 ◽  
Author(s):  
Gabriela P. Silote ◽  
Sabrina F.S. de Oliveira ◽  
Deidiane E. Ribeiro ◽  
Mayara S. Machado ◽  
Roberto Andreatini ◽  
...  
Keyword(s):  
Nmda Antagonist ◽  
Inhibitory Avoidance ◽  
Nmda Receptor Antagonist ◽  
Mixed Effects ◽  
Antidepressant Effect ◽  
List Type ◽  
Mk 801 ◽  
New Findings ◽  
Male Wistar Rats ◽  
Animal Tests

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

scholarly journals Prolonged Withdrawal from Escalated Oxycodone is Associated with Increased Expression of Glutamate Receptors in the Rat Hippocampus

2020 ◽  
Author(s):  
Aaron J Salisbury ◽  
Christopher A Blackwood ◽  
Jean Lud Cadet
Keyword(s):  
Glutamate Receptors ◽  
Molecular Mechanisms ◽  
Quantitative Polymerase Chain Reaction ◽  
Opioid Use Disorder ◽  
Mrna Levels ◽  
Opioid Use ◽  
Self Administration ◽  
Lever Pressing ◽  
Polymerase Chain ◽  
Long Access

People suffering from opioid use disorder (OUD) exhibit cognitive dysfunctions. Here, we investigated potential changes in the expression of glutamate receptors in rat hippocampi at 2 hours and 31 days after the last session of oxycodone self-administration (SA). RNA extracted from the hippocampus was used in quantitative polymerase chain reaction (qPCR) analyses. Rats, given long-access (9 hours per day) to oxycodone (LgA), took significantly more drug than rats exposed to short-access (3 hours per day) (ShA). In addition, LgA rats could be further divided into higher oxycodone taking (LgA-H) or lower oxycodone taking (LgA-L) groups, based on a cut-off of 50 infusions per day. LgA rats, but not ShA, rats exhibited incubation of oxycodone craving. In addition, LgA rats showed increased mRNA expression of GluA1-3 and GluN2a-c subunits as well as Grm3, Grm5, Grm6 and Grm8 subtypes of glutamate receptors after 31 days but not after 2 hours of stopping the SA experiment. Changes in GluA1-3, Grm6, and Grm8 mRNA levels also correlated with increased lever pressing (incubation) after long periods of withdrawal from oxycodone. More studies are needed to elucidate the molecular mechanisms involved in altering the expression of these receptors during withdrawal from oxycodone and/or incubation of drug seeking.

scholarly journals Stress vulnerability promotes an alcohol prone phenotype in a preclinical model of sustained depression

2018 ◽  
Author(s):  
Danai Riga ◽  
Leanne JM Schmitz ◽  
Yvar van Mourik ◽  
Witte JG Hoogendijk ◽  
Taco J De Vries ◽  
...  
Keyword(s):  
Social Defeat ◽  
Preclinical Model ◽  
Self Administration ◽  
Depression Vulnerability ◽  
Stress Vulnerability ◽  
The Social ◽  
Depression Proneness ◽  
Male Wistar Rats ◽  
Alcohol Seeking

AbstractMajor depression and alcohol-related disorders frequently co-occur. Depression severity weighs on the magnitude and persistence of comorbid alcohol use disorder (AUD), with severe implications for disease prognosis. Here, we investigated whether depression vulnerability drives propensity to AUD at the preclinical level. We used the social defeat-induced persistent stress (SDPS) model of chronic depression in combination with operant alcohol self-administration (SA). Male Wistar rats were subjected to social defeat (5 episodes) and prolonged social isolation (~12 weeks) and subsequently classified as SDPS-prone or SDPS-resilient based on their affective and cognitive performance. Using an operant alcohol SA paradigm, acquisition, motivation, extinction and cue-induced reinstatement of alcohol-seeking were examined in the two subpopulations. SDPS-prone animals showed increased alcohol SA, excessive motivation to acquire alcohol, persistent alcohol-seeking despite alcohol unavailability, extinction resistance and increased cue-induced relapse; the latter could be blocked by the α2 adrenoreceptor agonist guanfacine. In SDPS-resilient rats, prior exposure to social defeat increased alcohol SA without affecting any other measures of alcohol-seeking and -taking. Our data revealed that depression proneness confers vulnerability to alcohol, emulating patterns of alcohol dependence seen in human addicts, and that depression resilience to a large extent protects from the development of AUD-like phenotypes. Furthermore, our data suggest that stress exposure alone, independently of depressive symptoms, alters alcohol intake in the long-term.

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