scholarly journals Effects of Δ9-THC and cannabidiol vapor inhalation in male and female rats

2017 ◽  
Author(s):  
Mehrak Javadi-Paydar ◽  
Jacques D. Nguyen ◽  
Tony M. Kerr ◽  
Yanabel Grant ◽  
Sophia A. Vandewater ◽  
...  

AbstractRationalePrevious studies report sex differences in some, but not all, responses to cannabinoids in rats. The majority of studies use parenteral injection, however most human use is via smoke inhalation and, increasingly, vapor inhalation.ObjectivesTo compare thermoregulatory and locomotor responses to inhaled Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD) and their combination using an e-cigarette based model in male and female rats.MethodsMale and female Wistar rats (N=8 per group) were implanted with radiotelemetry devices for the assessment of body temperature and locomotor activity. Animals were then exposed to THC or CBD vapor using a propylene glycol (PG) vehicle. THC dose was adjusted via the concentration in the vehicle (12.5-200 mg/ml) and the CBD (100, 400 mg/mL) dose was also adjusted by varying the inhalation duration (10-40 minutes). Anti-nociception was evaluated using a tail-withdrawal assay following vapor inhalation. Plasma samples obtained following inhalation in different groups of rats were compared for THC content.ResultsTHC inhalation reduced body temperature and increased tail-withdrawal latency in both sexes equivalently and in a concentration-dependent manner. Female temperature, activity and tail-withdrawal responses to THC did not differ between the estrus and diestrus phases. CBD inhalation alone induced modest hypothermia and suppressed locomotor activity in both males and females. Co-administration of THC with CBD, in a 1:4 ratio, significantly decreased temperature and activity in an approximately additive manner and to similar extent in each sex. Plasma THC varied with the concentration in the PG vehicle but did not differ across rat sex.ConclusionIn summary the inhalation of THC or CBD, alone and in combination, produces approximately equivalent effects in male and female rats. This confirms the efficacy of the e-cigarette based method of THC delivery in female rats.

2020 ◽  
Author(s):  
Michael A Taffe ◽  
Jacques D Nguyen ◽  
Sophia A Vandewater ◽  
Yanabel Grant ◽  
Tobin J Dickerson

The α-pyrrolidino-phenone cathinone stimulants first came to widespread attention because of bizarre behavior consequent to the use of α-pyrrolidinopentiophenone (α-PVP, "flakka") reported in the popular press. As with other designer drugs, diversification of cathiones has been driven by desireable subjective effects, but also by attempts to stay ahead of legal controls of specific molecules. The α-pyrrolidinohexiophenone (α-PHP) and α-pyrrolidinopropiophenone (α-PPP) compounds have been relatively under-investigated relative to α-PVP and provide a key opportunity to also investigate structure-activity relationships, i.e., how the extension of the alpha carbon chain may affect potency or efficacy. Male and female rats were used to contrast the effects of α-PHP and α-PPP with those of α-PVP in altering wheel activity and effects on spontaneous locomotion and body temperature were assessed in female rats. The α-PHP and α-PVP compounds (5, 10 mg/kg, i.p.) suppressed wheel activity in female and male rats, whereas α-PPP was only effective in female rats. Inhalation of α-PHP or α-PVP by female rats suppressed wheel activity for an abbreviated duration, compared with the injection route. Spontaneous activity was increased in a dose-dependent manner by all three compounds in female rats, and a small decrements in body temperature were observed after the highest dose of all three compounds. These data show that all three of the α-pyrrolidino-phenone cathinones exhibit significant stimulant-like activity in both male and female rats. Differences were minor and were mostly in potency and the duration of activity. Abuse liability is therefore likely to be equivalent for all three pyrrolidino-phenones.


2021 ◽  
Author(s):  
Catherine F Moore ◽  
Elise M Weerts

Rationale The legalization of medicinal use of Cannabis sativa in most US states and the removal of hemp from the Drug Enforcement Agency (DEA) controlled substances act has resulted in a proliferation of products containing Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) for oral consumption (e.g., edibles, oils and tinctures) that are being used for recreational and medicinal purposes. Objective This study examined the effects of cannabinoids THC and CBD when administered orally on measures of pain sensitivity, body temperature, locomotor activity, and catalepsy (i.e., cannabinoid tetrad) in male and female Sprague Dawley rats. Methods Rats (N=24, 6 per sex/drug group) were administered THC (1-20 mg/kg), CBD (3-30 mg/kg), or sesame oil via oral gavage. Thermal and mechanical pain sensitivity (tail flick assay, von Frey test), rectal measurements for body temperature, locomotor activity, and the bar-test of catalepsy were completed. A separate group of rats (N=8/4 per sex) were administered morphine (5-20 mg/kg; intraperitoneal, IP) and evaluated for pain sensitivity as a positive control. Results We observed classic tetrad effects of antinociception, hypothermia, hyper- and hypolocomotion, and catalepsy after oral administration of THC that were long lasting (>7 hours). CBD modestly increased mechanical pain sensitivity and produced sex-dependent effects on body temperature and locomotor activity. Conclusions Oral THC and CBD produced long lasting effects, that differed in magnitude and time course when compared with other routes of administration. Examination of cannabinoid effects administered via different routes of administration, species, and in both males and females is critical to enhance translation.


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.


2008 ◽  
Vol 100 (6) ◽  
pp. 1192-1199 ◽  
Author(s):  
Pascale Rozan ◽  
Amine Nejdi ◽  
Sophie Hidalgo ◽  
Jean-François Bisson ◽  
Didier Desor ◽  
...  

Ageing is associated with changes in physiology and morphology; nutritional strategies to decrease morbidity and to prolong life are of high interest. The aim of the study was to investigate the effects of lifelong supplementation with an oligofructose-enriched inulin on morphological and biological markers and lifespan in male and female rats. Male and female rats, age 3 months, were randomised into two groups to receive either a diet with 10 % of an oligofructose-enriched inulin (Synergy1) or a standard diet (control) for 27 months. The rats were weighed every 2 weeks and their food intake was evaluated on four successive days every 4–6 weeks. Samples were taken at 12, 18 and 24 months of age. During the whole intervention period, male rats receiving Synergy1 (SYN1-M) displayed lower body weight, cholesterol and plasma triacylglycerolaemia compared with the controls (Cont-M). The survival rate at 24 months of age of SYN1-M rats was 35·3 % greater than that of Cont-M rats. In female rats, the Synergy1 supplementation (SYN1-F) group also reduced body weight, cholesterol and triacylglycerolaemia levels, but results were less consistent over the experiment. The survival rate at 24 months of age in SYN1-F rats was 33·3 % greater compared with that of the control (Cont-F) group. To conclude, lifelong intervention with Synergy1 improved biological markers during ageing and survival rate (lifespan) of rats.


1981 ◽  
Vol 90 (1) ◽  
pp. 41-51 ◽  
Author(s):  
J. A. F. TRESGUERRES ◽  
A. I. ESQUIFINO

Male and female Wistar rats were made hyperprolactinaemic by grafting two pituitary glands of litter-mate donors under the kidney capsule at 30 days of age. Other animals were sham-operated at the same age to serve as controls. Plasma levels of prolactin, LH and FSH were measured by double-antibody radioimmunoassay. Basal preoperative prolactin levels of ∼ 10 ng/ml increased after the transplantation in both male and female rats, reaching values of ∼ 180 ng/ml. Levels of LH were significantly reduced in these hyperprolactinaemic rats, whereas an increase in FSH values was seen. After administration of LH releasing hormone (LH-RH) a reduced LH response was seen but there was no response of FSH to LH-RH or even a decrease in FSH values. Prolactin levels were also reduced by LH-RH injection. Although an increase in prolactin levels was observed in control animals after a challenge with oestradiol benzoate, reduced increments were seen in experimental animals. The positive feedback effect of oestradiol benzoate on LH in females was reduced in pituitary-grafted rats but a potentiation of the FSH positive feedback could be clearly detected. This study suggests a dissociation of LH and FSH regulation in hyperprolactinaemia.


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.


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