scholarly journals The vagus nerve mediates the suppressing effects of peripherally administered oxytocin on methamphetamine self-administration and seeking in rats

2019 ◽  
Author(s):  
Nicholas A. Everett ◽  
Anita J Turner ◽  
Priscila A Costa ◽  
Sarah J. Baracz ◽  
Jennifer L. Cornish
Keyword(s):  
Clinical Trials ◽  
Vagus Nerve ◽  
Drug Withdrawal ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Self Administration ◽  
Male And Female ◽  
Functional Interactions ◽  
Sprague Dawley Rats ◽  
Suppressant Effect

AbstractBackgroundThe neuropeptide oxytocin has emerged as a promising pharmacotherapy for methamphetamine (METH) addiction, and clinical trials of intranasal oxytocin are underway. However, there is debate as to how peripherally administered oxytocin alters brain signaling to modulate addiction processes. Interestingly, there is evidence for functional interactions between peripheral oxytocin administration and the vagus nerve. Therefore, this study investigated whether the effects of peripherally administered oxytocin require vagal signaling to reduce METH self-administration and reinstatement of METH-seeking behaviours.MethodsMale and female Sprague-Dawley rats underwent surgery for jugular catheterization and either subdiaphragmatic vagotomy (SDV) or a sham operation. Rats were trained to self-administer METH, and the effect of peripherally administered oxytocin on METH intake was assessed. Rats then underwent extinction, and effects of oxytocin were assessed on cue- and METH-induced reinstatement of METH-seeking.ResultsOxytocin treatment robustly attenuated METH intake in both sexes. Strikingly, SDV entirely prevented the suppressant effect of oxytocin (0.3 mg/kg) on METH intake, and partially prevented the effects of 1 mg/kg oxytocin in both sexes. After extinction, SDV impaired the suppressing effects of oxytocin on cue- and METH-primed reinstatement in males, but not females. SDV was functionally confirmed by measuring food intake following administration of the vagal dependent peptide, cholecyostokin-8.ConclusionOur data suggest that vagus nerve signaling is required for the anti-addiction effects of peripherally administered oxytocin, and that this vagal dependency is partially mediated by sex and drug withdrawal. This study has considerable implications for the applicability of oxytocin as a therapy for METH use disorder for both sexes.

scholarly journals Absorption, Distribution, Excretion, and Pharmacokinetics ofC-Pyronaridine Tetraphosphate in Male and Female Sprague-Dawley Rats

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Sang Hyun Park ◽  
Kannampalli Pradeep
Keyword(s):  
Clinical Trials ◽  
Small Intestine ◽  
Oral Administration ◽  
Female Rats ◽  
Sprague Dawley ◽  
Male And Female ◽  
Phase Ii Clinical Trials ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
Peak Value

The main objective of this investigation was to determine the absorption, distribution, excretion, and pharmacokinetics of the antimalarial drug pyronaridine tetraphosphate (PNDP) in Sprague-Dawley rats. Following oral administration of a single dose (10 mg/Kg) ofC-PNDP, it was observed that the drug was readily absorbed from the small intestine within 1 hour following oral administration and was widely distributed in most of the tissues investigated as determined from the observed radioactivity in the tissues. The peak value of the drug in the blood was reached at around 8 hours postadministration, and radioactivity was detected in most of the tissues from 4 hours onwards.C-PNDP showed a poor permeability across the blood-brain barrier, and the absorption, distribution, and excretion ofC-PNDP were found to be gender-independent as both male and female rats showed a similar pattern of radioactivity. Excretion of the drug was predominantly through the urine with a peak excretion post 24 hours of administration. A small amount of the drug was also excreted in the feces and also in the breath. It was found that theCmax, AUC (0-inf), andTmaxvalues were similar to those observed in the Phase II clinical trials of pyronaridine/artesunate (Pyramax) conducted in Uganda.

Ultrastructural investigation of spontaneous pituitary gonadotroph cell adenomas in aging Sprague-Dawley rats

1983 ◽  
Vol 41 ◽  
pp. 702-703
Author(s):  
D. J. McComb ◽  
J. Beri ◽  
F. Zak ◽  
K. Kovacs
Keyword(s):  
Electron Microscopy ◽  
Animal Model ◽  
Epoxy Resin ◽  
Immunoelectron Microscopy ◽  
Tumor Type ◽  
Gonadal Function ◽  
Sprague Dawley ◽  
Male And Female ◽  
Reticulin Fibers ◽  
Sprague Dawley Rats

Gonadotroph cell adenomas of the pituitary are infrequent in human patients and are not invariably associated with altered gonadal function. To date, no animal model of this tumor type exists. Herein, we describe spontaneous gonadotroph cell adenomas in old male and female Sprague-Dawley rats by histology, immunocytology and electron microscopy.The material consisted of the pituitaries of 27 male and 38 female Sprague Dawley rats, all 26 months of age or older, removed at routine autopsy. Sections of formal in-fixed, paraffin-embedded tissue were stained with hematoxylin-phloxine-saffron (HPS), the PAS method and the Gordon-Sweet technique for the demonstration of reticulin fibers. For immunostaining, sections were exposed to anti-rat β-LH, anti-ratβ-TSH, anti-rat PRL, anti-rat GH and anti-rat ACTH 1-39. For electron microscopy, tissue was fixed in 2.5% glutaraldehyde, postfixed in 1% OsO4 and embedded in epoxy-resin. Tissue fixed in 10% formalin, embedded in epoxy resin without osmification, was used for immunoelectron microscopy.

Hepatic effects of a highly purified PCB 180 in adult male and female Sprague–Dawley rats

2008 ◽  
Vol 180 ◽  
pp. S39-S40
Author(s):  
Robert Roos ◽  
Patrik Andersson ◽  
Päivi Heikkinen ◽  
Hans-Joachim Schmitz ◽  
Leo van der Ven ◽  
...  
Keyword(s):  
Adult Male ◽  
Sprague Dawley ◽  
Male And Female ◽  
Sprague Dawley Rats

scholarly journals Effects of adolescent caffeine consumption on cocaine self-administration and reinstatement of cocaine seeking

2018 ◽  
Vol 33 (1) ◽  
pp. 132-144
Author(s):  
Tracey A Larson ◽  
Casey E O’Neill ◽  
Michaela P Palumbo ◽  
Ryan K Bachtell
Keyword(s):  
Dose Response ◽  
Extinction Training ◽  
Schedules Of Reinforcement ◽  
Sprague Dawley ◽  
Self Administration ◽  
Caffeine Consumption ◽  
Adult Rats ◽  
Sprague Dawley Rats ◽  
Cocaine Seeking ◽  
Administration Procedure

Background: Caffeine consumption by children and adolescents has risen dramatically in recent years, yet the lasting effects of caffeine consumption during adolescence remain poorly understood. Aim: These experiments explore the effects of adolescent caffeine consumption on cocaine self-administration and seeking using a rodent model. Methods: Sprague-Dawley rats consumed caffeine for 28 days during the adolescent period. Following the caffeine consumption period, the caffeine solution was replaced with water for the remainder of the experiment. Age-matched control rats received water for the duration of the study. Behavioral testing in a cocaine self-administration procedure occurred during adulthood (postnatal days 62–82) to evaluate how adolescent caffeine exposure influenced the reinforcing properties of cocaine. Cocaine seeking was also tested during extinction training and reinstatement tests following cocaine self-administration. Results: Adolescent caffeine consumption increased the acquisition of cocaine self-administration and increased performance on different schedules of reinforcement. Consumption of caffeine in adult rats did not produce similar enhancements in cocaine self-administration. Adolescent caffeine consumption also produced an upward shift in the U-shaped dose response curve on cocaine self-administration maintained on a within-session dose-response procedure. Adolescent caffeine consumption had no effect on cocaine seeking during extinction training or reinstatement of cocaine seeking by cues or cocaine. Conclusions: These findings suggest that caffeine consumption during adolescence may enhance the reinforcing properties of cocaine, leading to enhanced acquisition that may contribute to increased addiction vulnerability.

Relative equivalence of CNS safety (FOB) assessment outcomes in male and female Wistar-Han and Sprague-Dawley rats

2019 ◽  
Vol 95 ◽  
pp. 2-11 ◽  
Author(s):  
David V. Gauvin ◽  
Jill A. Dalton ◽  
Marci L. Harter ◽  
David Holdsworth ◽  
Jonelle May ◽  
...  
Keyword(s):  
Sprague Dawley ◽  
Male And Female ◽  
Sprague Dawley Rats ◽  
Assessment Outcomes

Ammonia reduction with ornithine phenylacetate restores brain eNOS activity via the DDAH-ADMA pathway in bile duct-ligated cirrhotic rats

2012 ◽  
Vol 302 (1) ◽  
pp. G145-G152 ◽  
Author(s):  
Vairappan Balasubramaniyan ◽  
Gavin Wright ◽  
Vikram Sharma ◽  
Nathan A. Davies ◽  
Yalda Sharifi ◽  
...  
Keyword(s):  
Bile Duct ◽  
Protein Expression ◽  
Ammonia Concentration ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Duct Ligation ◽  
Tnf Α ◽  
No Signaling ◽  
Brain Water

Ammonia is central in the pathogenesis of hepatic encephalopathy, which is associated with dysfunction of the nitric oxide (NO) signaling pathway. Ornithine phenylacetate (OP) reduces hyperammonemia and brain water in cirrhotic animals. This study aimed to determine whether endothelial NO synthase activity is altered in the brain of cirrhotic animals, whether this is associated with changes in the endogenous inhibitor, asymmetric-dimethylarginine (ADMA) and its regulating enzyme, dimethylarginine-dimethylaminohydrolase (DDAH-1), and whether these abnormalities are restored by ammonia reduction using OP. Sprague-Dawley rats were studied 4-wk after bile duct ligation (BDL) ( n = 16) or sham operation ( n = 8) and treated with placebo or OP (0.6 g/kg). Arterial ammonia, brain water, TNF-α, plasma, and brain ADMA were measured using standard techniques. NOS activity was measured radiometrically, and protein expression for NOS enzymes, ADMA, DDAH-1, 4-hydroxynonenol (4HNE), and NADPH oxidase (NOX)-1 were measured by Western blotting. BDL significantly increased arterial ammonia ( P < 0.0001), brain water ( P < 0.05), and brain TNF-α ( P < 0.01). These were reduced significantly by OP treatment. The estimated eNOS component of constitutive NOS activity was significantly lower ( P < 0.05) in BDL rat, and this was significantly attenuated in OP-treated animals. Brain ADMA levels were significantly higher and brain DDAH-1 significantly lower in BDL compared with sham ( P < 0.01) and restored toward normal following treatment with OP. Brain 4HNE and NOX-1 protein expression were significantly increased in BDL rat brain, which were significantly decreased following OP administration. We show a marked abnormality of NO regulation in cirrhotic rat brains, which can be restored by reduction in ammonia concentration using OP.

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