Binge-like Acquisition of α-pyrrolidinopentiophenone (α-PVP) Self-Administration in Female Rats

Mapping Intimacies ◽

10.1101/191155 ◽

2017 ◽

Author(s):

Mehrak Javadi-Paydar ◽

Eric L. Harvey ◽

Yanabel Grant ◽

Sophia A. Vandewater ◽

Kevin M. Creehan ◽

...

Keyword(s):

Activity Wheel ◽

Female Rats ◽

Dose Effect ◽

Male Rats ◽

Self Administration ◽

Female Wistar Rats ◽

Public Behavior ◽

Related Drug ◽

Synthetic Cathinone ◽

Wheel Activity

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.

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

10.1101/166579 ◽

2017 ◽

Author(s):

Mehrak Javadi-Paydar ◽

Jacques D. Nguyen ◽

Sophia A. Vandewater ◽

Tobin J. Dickerson ◽

Michael A. Taffe

Keyword(s):

Wistar Rats ◽

Second Generation ◽

Female Rats ◽

Dose Effect ◽

Male Rats ◽

Structural Motif ◽

Self Administration ◽

Male And Female ◽

Female Wistar Rats ◽

Reinforcing Effects

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.

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Sex Differences in Escalated Methamphetamine Self-Administration and Altered Gene Expression Associated With Incubation of Methamphetamine Seeking

The International Journal of Neuropsychopharmacology ◽

10.1093/ijnp/pyz050 ◽

2019 ◽

Vol 22 (11) ◽

pp. 710-723 ◽

Cited By ~ 8

Author(s):

Atul P Daiwile ◽

Subramaniam Jayanthi ◽

Bruce Ladenheim ◽

Michael T McCoy ◽

Christie Brannock ◽

...

Keyword(s):

Sex Differences ◽

Nucleus Accumbens ◽

Fixed Ratio ◽

Female Rats ◽

Male Rats ◽

Mrna Levels ◽

Self Administration ◽

Male And Female ◽

Orexin Receptors ◽

Male And Female Rats

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.

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Hypothalamo-pituitary regulation of the c-myc gene in rat liver

Journal of Molecular Endocrinology ◽

10.1677/jme.0.0050267 ◽

1990 ◽

Vol 5 (3) ◽

pp. 267-274 ◽

Cited By ~ 5

Author(s):

I. Porsch Hällstöm ◽

J.-Å. Gustafsson ◽

A. Blanck

Keyword(s):

Rat Liver ◽

Female Rats ◽

Male Rats ◽

Female Rat ◽

Continuous Administration ◽

Gh Secretion ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation ◽

Female Wistar Rats ◽

Myc Gene

ABSTRACT Expression of the c-myc gene was studied in the livers of male and female Wistar rats. Furthermore, the effects on hepatic c-myc expression of neonatal and adult castration, with or without testosterone supplementation, as well as of continuous administration of GH to intact males, were analysed. Expression of c-myc was low in 6-day-old animals of both sexes, reached a maximum at 35 days of age and declined to the level of adult animals at 70 days. In prepubertal animals, expression was higher in females, but was higher in males after the onset of puberty, the postpubertal female rat liver exhibiting 50–70% of the expression in males. Treatment of adult male rats with bovine GH in osmotic minipumps for 1 week reduced c-myc expression to the level of female rats. Castration, both neonatally and of adults, also feminized hepatic c-myc expression. Testosterone supplementation of the castrated animals increased the expression towards the level in sham-operated controls. These results indicate that the c-myc gene is regulated by the hypothalamo-pituitary-liver axis via the sex-differentiated pattern of GH secretion, in analogy with other sex-differentiated hepatic functions, such as metabolism of steroids and xenobiotics. Neuroendocrine regulation of a gene such as c-myc, which is involved in the control of cell proliferation and differentiation, represents another aspect of the complex influence of GH on various somatic functions.

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Hydration with Mannitol and Dextrose May Promote Cisplatin-Induced Nephrotoxicity: Test of Five Protocols of Hydration during Cisplatin Therapy in Rat Models

Journal of Toxicology ◽

10.1155/2021/5547341 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Mohammad-Sedigh Khosravi ◽

Alireza Samimiat ◽

Bahar Mazaheri ◽

Farzaneh Ashrafi ◽

Ardeshir Talebi ◽

...

Keyword(s):

Tumor Therapy ◽

Kidney Tissue ◽

Serum Levels ◽

Female Rats ◽

Male Rats ◽

Male And Female ◽

Male And Female Rats ◽

Female Wistar Rats ◽

Solid Tumor Therapy ◽

Cisplatin Therapy

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.

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Sex- and age-dependent differences in the hormone and drinking responses to water deprivation

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00303.2019 ◽

2020 ◽

Vol 318 (3) ◽

pp. R567-R578 ◽

Cited By ~ 2

Author(s):

Susana Quirós Cognuck ◽

Wagner L. Reis ◽

Marcia S. Silva ◽

Gislaine Almeida-Pereira ◽

Lucas K. Debarba ◽

...

Keyword(s):

Water Deprivation ◽

Plasma Concentrations ◽

Female Rats ◽

Male Rats ◽

Ang Ii ◽

Adult Males ◽

Adaptive Responses ◽

Male And Female ◽

Male And Female Rats ◽

Female Wistar Rats

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.

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An analysis of the course of infection of Moniliformis dubius (Acanthocephala) in rats

Parasitology ◽

10.1017/s0031182000045583 ◽

1972 ◽

Vol 64 (3) ◽

pp. 517-523 ◽

Cited By ~ 28

Author(s):

D. W. T. Crompton ◽

D. E. Walters

Keyword(s):

Wistar Rats ◽

Female Rats ◽

Male Rats ◽

Male And Female ◽

Oral Infections ◽

The Third ◽

Male And Female Rats ◽

Female Wistar Rats ◽

Average Recovery Rate ◽

Marked Decline

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.

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Tolerance to hypothermic and antinoceptive effects of Δ9-tetrahydrocannabinol (THC) vapor inhalation in rats

10.1101/172759 ◽

2017 ◽

Author(s):

Jacques D. Nguyen ◽

Yanabel Grant ◽

Tony M. Kerr ◽

Arnold Gutierrez ◽

Maury Cole ◽

...

Keyword(s):

Propylene Glycol ◽

Wistar Rats ◽

Female Rats ◽

Male Rats ◽

Preclinical Studies ◽

Male And Female ◽

Temperature Changes ◽

Male And Female Rats ◽

Antinociceptive Effects ◽

Female Wistar Rats

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;

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7,8-Dihydroxyflavone Enhances Cue-Conditioned Alcohol Reinstatement in Rats

Brain Sciences ◽

10.3390/brainsci10050270 ◽

2020 ◽

Vol 10 (5) ◽

pp. 270 ◽

Cited By ~ 1

Author(s):

Samuel J. Hogarth ◽

Elvan Djouma ◽

Maarten van den Buuse

Keyword(s):

Body Weight ◽

Progressive Ratio ◽

Ethanol Exposure ◽

Ethanol Solution ◽

Female Rats ◽

Male Rats ◽

Sprague Dawley ◽

Self Administration ◽

Bdnf Expression ◽

Sprague Dawley Rats

Alcohol use disorder (AUD) is a detrimental disease that develops through chronic ethanol exposure. Reduced brain-derived neurotrophic factor (BDNF) expression has been associated with AUD and alcohol addiction, however the effects of activation of BDNF signalling in the brain on voluntary alcohol intake reinstatement and relapse are unknown. We therefore trained male and female Sprague Dawley rats in operant chambers to self-administer a 10% ethanol solution. Following baseline acquisition and progressive ratio (PR) analysis, rats were split into drug and vehicle groups during alcohol lever extinction. The animals received two weeks of daily IP injection of either the BDNF receptor, TrkB, agonist, 7,8-dihydroxyflavone (7,8-DHF), or vehicle. During acquisition of alcohol self-administration, males had significantly higher absolute numbers of alcohol-paired lever presses and a higher PR breakpoint. However, after adjusting for body weight, the amount of ethanol was not different between the sexes and the PR breakpoint was higher in females than males. Following extinction, alcohol-primed reinstatement in male rats was not altered by pretreatment with 7,8-DHF when adjusted for body weight. In contrast, in female rats, the weight-adjusted potential amount of ethanol, but not absolute numbers of active lever presses, was significantly enhanced by 7,8-DHF treatment during reinstatement. Analysis of spontaneous locomotor activity in automated photocell cages suggested that the effect of 7,8-DHF was not associated with hyperactivity. These results suggest that stimulation of the TrkB receptor may contribute to reward craving and relapse in AUD, particularly in females.

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Body Adiposity and Endocrine Profile of Female Wistar Rats of Distinct Ages that were Early Weaned

Hormone and Metabolic Research ◽

10.1055/a-0966-8784 ◽

2019 ◽

Vol 52 (01) ◽

pp. 58-66 ◽

Cited By ~ 1

Author(s):

Carla Bruna Pietrobon ◽

Iala Milene Bertasso ◽

Beatrix S. Silva ◽

Nayara Peixoto-Silva ◽

Elaine Oliveira ◽

...

Keyword(s):

Vitamin D ◽

Body Fat ◽

Female Rats ◽

Male Rats ◽

Fat Percentage ◽

Fat Depots ◽

Lower Body Weight ◽

Female Wistar Rats ◽

Endocrine Profile ◽

And Control

AbstractEarly weaning (EW) is a risk factor for metabolic syndrome. Male rats that were precociously weaned present neonatal malnutrition and, in adulthood, developed overweight, accumulation of body fat, dyslipidemia, changes in glycemic homeostasis, hyperleptinemia, and increase of vitamin D. As metabolic profile of early-weaned females is not known, we investigated the endocrine-metabolic parameters in adolescence and adult female rats of 2 different EW models. Wistar lactating rats and pups from both sexes were separated into 3 groups: non-pharmacological EW (NPEW), dams were involved with a bandage interrupting suckling in the last 3 days of lactation; pharmacological EW (PEW), dams were bromocriptine-treated (0.5 mg/twice a day via intraperitoneal injection) for 3 days before weaning; and control, dams whose pups ate milk throughout lactation. At 21 days-old, NPEW and PEW females had lower body weight. At 180 days-old, NPEW and PEW females showed higher feed efficiency, weight gain, body fat percentage, and greater accumulation of gonadal and retroperitoneal fat depots associated with adipocyte hypertrophy. NPEW females also showed hyperphagia. Only NPEW females presented hyperleptinemia. Plasma thyroid hormones and vitamin D were unchanged among EW females. Regarding sex hormones, at 45 days-old, no change was found in EW females, while at 180 days-old, PEW females had hypoestrogenemia. EW increases the risk for obesity in female rats in adulthood, as already demonstrated for males, although through distinct mechanisms involving some hormones.

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