scholarly journals Locomotor and Reinforcing Effects of Pentedrone, Pentylone and Methylone in Rats

2017 ◽  
Author(s):  
Mehrak Javadi-Paydar ◽  
Jacques D. Nguyen ◽  
Sophia A. Vandewater ◽  
Tobin J. Dickerson ◽  
Michael A. Taffe

AbstractThe broad diversity of synthetic cathinone psychostimulant drugs that are available to users complicates research efforts to provide understanding of health risks. Second generation cathinones pentedrone and pentylone are distinguished from each other by the 3,4-methylenedioxy structural motif (which distinguishes methamphetamine from 3,4-methylenedioxymethamphetamine) and each incorporates the α-alkyl chain motif contained in the transporter-inhibitor cathinones (3,4-methylenedioxypyrovalerone (MDPV), α-pyrrolidinopentiophenone (α-PVP)) but not in the monoamine releasers (mephedrone, methylone). Studies were conducted in male and female Wistar rats to compare locomotor and thermoregulatory effects of pentedrone, pentylone and methylone using an implanted radiotelemetry system. Reinforcing effects were assessed in female Wistar rats trained in the intravenous self-administration (IVSA) procedure and subjected to dose-substitution (0.025-0.3 m/gkg/inf) under a fixed-ratio 1 response contingency. Pentedrone, pentylone and methylone dose-effect curves were contrasted with those for α-PVP and α-pyrrolidinohexiophenone (α-PHP). Dose dependent increases in locomotion were observed after intraperitoneal injection of pentylone (0.5-10.0 mg/kg), pentedrone (0.5-10.0 mg/kg) or mephedrone (0.5-10.0 mg/kg) in male and female rats. The maximum locomotor effect was similar across drugs but lasted longest after pentedrone. Mean body temperature did not vary systematically more than 0.5 °C after pentedrone or pentylone in either sex. A sustained hyperthermia (0.4-0.8 °C) was observed for four hours after 10 mg/kg methylone in male rats. More infusions of pentedrone or pentylone were self-administered compared with methylone, but all three were less potent than α-PVP or α-PHP. These studies support the inference that second generation cathinones pentylone and pentedrone have abuse liability greater than that of methylone.

Parasitology ◽  
1972 ◽  
Vol 64 (3) ◽  
pp. 517-523 ◽  
Author(s):  
D. W. T. Crompton ◽  
D. E. Walters

An analysis of the course of infection of mixed oral infections of 12 cystacanths of Moniliformis dubius in 174 male and 179 female Wistar rats has been undertaken.There was a marked decline in the average recovery rate of worms of both sexes from hosts of both sexes during the course of the infection.Female worms from both male and female rats showed, on average, a greater power of survival than male worms from the third period (10–13 weeks) onwards.Male rats were found to retain, on average, a greater number of worms of both sexes than female rats.We wish to thank Miss Susan Arnold and Mr David Barnard for excellent technical help.


2017 ◽  
Author(s):  
Jacques D. Nguyen ◽  
Yanabel Grant ◽  
Tony M. Kerr ◽  
Arnold Gutierrez ◽  
Maury Cole ◽  
...  

AbstractRationaleA reduced effect of a given dose of Δ9-tetrahydrocannabinol (THC) emerges with repeated exposure to the drug. This tolerance can vary depending on THC dose, exposure chronicity and the behavioral or physiological measure of interest. A novel THC inhalation system based on e-cigarette technology has been recently shown to produce the hypothermic and antinociceptive effects of THC in rats.ObjectiveTo determine if tolerance to these effects can be produced with repeated vapor inhalation.MethodsGroups of male and female Wistar rats were exposed to 30 minutes of inhalation of the propylene glycol (PG) vehicle or THC (200 mg/mL in PG) two or three times per day for four days. Rectal temperature changes and nociception were assessed after the first exposure on the first and fourth days of repeated inhalation.ResultsFemale, but not male, rats developed tolerance to the hypothermic and antinociceptive effects of THC after four days of twice-daily THC vapor inhalation. Thrice daily inhalation for four days resulted in tolerance in both male and female rats. The plasma THC levels reached after a 30 minute inhalation session did not differ between the male and female rats.ConclusionsRepeated daily THC inhalation induces tolerance in female and male rats, providing further validation of the vapor inhalation method for preclinical studies.AbbreviationsPG, propylene glycol; THC; Δ9tetrahydrocannabinol;


1994 ◽  
Vol 267 (6) ◽  
pp. H2311-H2317 ◽  
Author(s):  
K. Kauser ◽  
G. M. Rubanyi

Gender differences in the production/release of endothelium-derived nitric oxide (EDNO) was assessed by determining the ability of intact endothelium to suppress serotonin- (10(-7)-10(-5) M) and phenylephrine-induced (10(-9)-(10(-5) M) contractions in thoracic aortae isolated from male and female Wistar rats mounted in organ chambers for isometric tension recording or tested in bioassay experiments. The endothelium suppressed these contractions significantly more in aortae from female than from male rats. In the bioassay, the perfusate from intact female thoracic aortic segments produced a significantly greater relaxation of the detector rings than that from the aortae isolated from male rats. Acetylcholine (10(-9)-10(-5) M), used to investigate agonist-induced release of EDNO, evoked significantly greater endothelium-dependent relaxation in aortae from female rats. The unstimulated release of 6-ketoprostaglandin F1 alpha and thromboxane B2 from intact thoracic aortic rings from male and female rats was not significantly different. There was no difference in smooth muscle reactivity to sodium nitroprusside (10(-10)-10(-6) M) in rings without endothelium. These results indicate that EDNO production/release is higher in thoracic aortae isolated from female rats.


Author(s):  
Lynda AÏNOUZ ◽  
Mohamed ZAOUANI ◽  
Hayat REMICHI ◽  
Sofiane BOUDJELLABA ◽  
Kahina CHABANE ◽  
...  

Cardiovascular disease (CVD) are mainly consequent of atherosclerosis.  Men develop CVD at a young age, this risk increases in women at an older age. Several studies have been carried out on male rats, but experiments on growing rats especially female are rare.  The objective of this study was to investigate the effect of a high cholesterol and high fructose diet on the coronary artery and myocardium in growing male and female rats Young Wistar rats were divided into control groups fed a standard diet, cholesterol groups supplemented with 3% cholesterol (ChD), and cholesterol-fructose groups supplemented with 3% cholesterol and 15% fructose (ChFrD) for 14 weeks. Each group consists of male (n=6) and female (n=6) rats.   We found, in comparison with corresponding controls rats, that both ChD and ChFrD diets caused a significant hyperglycemia and dyslipidaemia. In hearts supernatants, we highlighted increases of total lipids, malondialdehyde and Catalase assays. The histopathological examination showed a disorganization of the myocardial structure, arterial walls damage and endothelium injuries. Our study showed that ChD and ChFrD diets, caused weight, biochemical, oxidative and tissue disturbances that could lead to CVD in both young male and female Wistar rats even during the growing period.


2017 ◽  
Author(s):  
Mehrak Javadi-Paydar ◽  
Eric L. Harvey ◽  
Yanabel Grant ◽  
Sophia A. Vandewater ◽  
Kevin M. Creehan ◽  
...  

AbstractThe synthetic cathinone α-pyrrolidinopentiophenone (α-PVP) has been associated with violent and/or bizarre public behavior in users. Association of such behavior with extended binges of drug use motivates additional investigation, particularly since a prior study found that half of male rats experience a binge of exceptionally high intake, followed by sustained lower levels of self-administration during the acquisition of intravenous self-administration (IVSA) of a closely related drug, 3,4-methylenedioxypyrovalerone. The binge-like acquisition pattern appeared to be novel for rat IVSA, thus the present study was designed to determine if this effect generalizes to IVSA of α-PVP in female rats. Female Wistar rats were trained in IVSA of α-PVP (0.05 mg/kg/inf) in experimental chambers that contained an activity wheel. Groups of animals were trained with the wheels fixed (No-Wheel group), fixed for the initial 5 days of acquisition or free to move throughout acquisition (Wheel group). The groups were next subjected to a wheel-access switch and then all animals to dose-substitution (0.0125-0.3 mg/kg/inf) with the wheels alternately fixed and free to move. Approximately half of the rats initiated their IVSA pattern with a binge day of exceptionally high levels of drug intake, independent of wheel access condition. Wheel activity was much lower in the No-Wheel group in the wheel switch post-acquisition. Dose-effect curves were similar for wheel-access training groups, for binge/no binge phenotypic subgroups and were not altered with wheel access during the dose-substitution. This confirms the high reinforcer efficacy of α-PVP in female rats and the accompanying devaluation of wheel activity as a naturalistic reward.


2019 ◽  
Vol 22 (11) ◽  
pp. 710-723 ◽  
Author(s):  
Atul P Daiwile ◽  
Subramaniam Jayanthi ◽  
Bruce Ladenheim ◽  
Michael T McCoy ◽  
Christie Brannock ◽  
...  

Abstract Background Methamphetamine (METH) use disorder is prevalent worldwide. There are reports of sex differences in quantities of drug used and relapses to drug use among individuals with METH use disorder. However, the molecular neurobiology of these potential sex differences remains unknown. Methods We trained rats to self-administer METH (0. 1 mg/kg/infusion, i.v.) on an fixed-ratio-1 schedule for 20 days using two 3-hour daily METH sessions separated by 30-minute breaks. At the end of self-administration training, rats underwent tests of cue-induced METH seeking on withdrawal days 3 and 30. Twenty-four hours later, nucleus accumbens was dissected and then used to measure neuropeptide mRNA levels. Results Behavioral results show that male rats increased the number of METH infusions earlier during self-administration training and took more METH than females. Both male and female rats could be further divided into 2 phenotypes labeled high and low takers based on the degree of escalation that they exhibited during the course of the METH self-administration experiment. Both males and females exhibited incubation of METH seeking after 30 days of forced withdrawal. Females had higher basal mRNA levels of dynorphin and hypocretin/orexin receptors than males, whereas males expressed higher vasopressin mRNA levels than females under saline and METH conditions. Unexpectedly, only males showed increased expression of nucleus accumbens dynorphin after METH self-administration. Moreover, there were significant correlations between nucleus accumbens Hcrtr1, Hcrtr2, Crhr2, and Avpr1b mRNA levels and cue-induced METH seeking only in female rats. Conclusion Our results identify some behavioral and molecular differences between male and female rats that had self-administered METH. Sexual dimorphism in responses to METH exposure should be considered when developing potential therapeutic agents against METH use disorder.


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Mohammad-Sedigh Khosravi ◽  
Alireza Samimiat ◽  
Bahar Mazaheri ◽  
Farzaneh Ashrafi ◽  
Ardeshir Talebi ◽  
...  

Backgrounds. Cisplatin (CP) still is a novel choice for solid tumor therapy, but it is accompanied with the side effect of nephrotoxicity. Hydration may reduce the risk of CP-induced nephrotoxicity, while the issue is still challenging. In this study, five types of hydration protocols including saline, mannitol, dextrose saline, saline plus furosemide, and saline plus mannitol were examined in both sexes of rats during CP therapy. Methods. Seventy-six male and female Wistar rats in 14 groups of experiments were subjected to CP therapy, and five types of hydration protocols were implemented, and the induced nephrotoxicity was evaluated via biochemical markers, kidney function parameters, and pathology investigation. Results. Male and female rats had different responses to hydration protocol types. The higher mortality rate was seen in female rats that received mannitol or dextrose hydration types. In addition, the serum levels of blood urea nitrogen (BUN) and creatinine (Cr) and sodium excretion fraction (ENa%) increased and the clearance of Cr (ClCr) decreased significantly ( P < 0.05 ) in female rats hydrated with saline plus furosemide or mannitol plus saline-treated groups. The worsened condition in male rats is observed in the mannitol hydration group with a significant decrease of ClCr and significant increase of serum BUN and Cr and ENa% ( P < 0.05 ). The higher kidney tissue damage score (KTDS) in the mentioned groups verified the findings. Conclusion. Hydration with mannitol or dextrose promotes the risk of nephrotoxicity during CP therapy with more intensity on the female.


2020 ◽  
Vol 318 (3) ◽  
pp. R567-R578 ◽  
Author(s):  
Susana Quirós Cognuck ◽  
Wagner L. Reis ◽  
Marcia S. Silva ◽  
Gislaine Almeida-Pereira ◽  
Lucas K. Debarba ◽  
...  

Maintenance of the volume and osmolality of body fluids is important, and the adaptive responses recruited to protect against osmotic stress are crucial for survival. The objective of this work was to compare the responses that occur in aging male and female rats during water deprivation. For this purpose, groups of male and female Wistar rats aged 3 mo (adults) or 18 mo (old) were submitted to water deprivation (WD) for 48 h. The water and sodium (0.15 M NaCl) intake, plasma concentrations of oxytocin (OT), arginine vasopressin (AVP), corticosterone (CORT), atrial natriuretic peptide (ANP), and angiotensin II (ANG II) were determined in hydrated and water-deprived animals. In response to WD, old male and female rats drank less water and saline than adults, and both adult and old females drank more water and saline than respective males. Dehydrated old animals displayed lower ANG II plasma concentration and CORT response compared with the respective normohydrated rats. Dehydrated adult males had higher plasma ANP and AVP as well as lower CORT concentrations than dehydrated adult females. Moreover, plasma OT and CORT levels of old female rats were higher than those in the dehydrated old male rats. Relative expression of ANG II type 1 receptor mRNA was decreased in the subfornical organ of adult and old male rats as well as adult female rats in response to WD. In conclusion, the study elucidated the effect of sex and age on responses induced by WD, altering the degree of dehydration induced by 48 h of WD.


1990 ◽  
Vol 68 (10) ◽  
pp. 1385-1387 ◽  
Author(s):  
Viviana A. Catania ◽  
Marcelo G. Luquita ◽  
María C. Carrillo ◽  
Aldo D. Mottino

In the present study we analyzed the effect of spironolactone administration on hepatic and intestinal p-nitrophenol-UDP-glucuronyltransferase activity. We used microsomal preparations from male and female Wistar rats to establish whether or not this effect was sex dependent. Enzyme activity was measured in the presence of UDP-N-acetylglucosamine, a presumed physiological activator of the enzyme. Female but not male microsomes showed an increase in enzyme activity of both hepatic and intestinal tissue preparations in response to the inducer pretreatment. In addition, the inducer effect observed in female rats showed a tissue-related difference, since percent increase in the intestinal enzyme activity was greater than that in the liver (127 and 52%, respectively). These results suggest that factors regulating enzyme activity or mechanisms involved in the inducer effect of spironolactone could be different in the intestinal mucosa in comparison to the liver. A possible explanation of sex-related response to spironolactone administration was discussed.Key words: p-nitrophenol, UDP-glucuronyltransferase, spironolactone induction, sex differences.


2011 ◽  
Vol 30 (6) ◽  
pp. 662-670 ◽  
Author(s):  
Kottarapat Jeena ◽  
Vijayastelter B. Liju ◽  
Ramadasan Kuttan

Zingiber officinale Roscoe, ginger, is a major spice extensively used in traditional medicine. The toxicity profile of ginger oil was studied by subchronic oral administration for 13 weeks at doses of 100, 250, and 500 mg/kg per day to 6 groups of Wistar rats (5/sex per dose). Separate groups of rats (5/sex per group) received either paraffin oil (vehicle) or were untreated and served as comparative control groups. There was no mortality and no decrease in body weight or food consumption as well as selective organ weights during the study period. Administration of ginger oil to rats did not produce any treatment-related changes in hematological parameters, hepatic, renal functions, serum electrolytes, or in histopathology of selected organs. The major component of ginger oil was found to be zingiberene (31.08%), and initial studies indicated the presence of zingiberene in the serum after oral dosing. These results confirmed that ginger oil is not toxic to male and female rats following subchronic oral administrations of up to 500 mg/kg per day (no observed adverse effect level [NOAEL]).


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