scholarly journals Advanced age attenuates the antihyperalgesic effect of morphine and decreases μ-opioid receptor expression and binding in the rat midbrain Periaqueductal Gray in male and female rats

2020 ◽  
Author(s):  
Evan F. Fullerton ◽  
Myurajan Rubaharan ◽  
Mary C. Karom ◽  
Richard I. Hanberry ◽  
Anne Z. Murphy

AbstractThe present study investigated the impact of advanced age on morphine modulation of persistent inflammatory pain in male and female rats. The impact of age, sex, and pain on μ-opioid receptor (MOR) expression and binding in the ventrolateral PAG (vlPAG) was also examined using immunohistochemistry and receptor autoradiography. Intraplantar administration of Complete Freund’s adjuvant induced comparable levels of edema and hyperalgesia in adult (2-3mos) and aged (16-18mos) male and female rats. Morphine potency was highest in adult males, with a two-fold decrease in morphine EC50 observed in aged versus adult males (10.22mg/kg versus 5.19mg/kg). Adult and aged female rats also exhibited significantly higher EC50 values (10.69 mg/kg and 9.00 mg/kg, respectively) compared to adult males. The upward shift in EC50 from adult to aged males was paralleled by a reduction in vlPAG MOR expression and binding. The observed age-related reductions in morphine potency and vlPAG MOR expression and binding have significant implications in pain management in the aged population.

2007 ◽  
Vol 2007 ◽  
pp. 1-12 ◽  
Author(s):  
Maria Toledo-Rodriguez ◽  
Carmen Sandi

Adolescence is a period of major physical, hormonal, and psychological changes. It is also characterized by a significant increase in the incidence of psychopathologies and this increase is gender-specific. Stress during adolescence is associated with the development of psychiatric disorders later in life. In this study, we evaluated the impact of psychogenic stress (exposure to predator odor followed by placement on an elevated platform) experienced before puberty (days 28–30) on fear memories and hormonal response of male and female rats during adolescence and early adulthood. Stress before puberty impacted in a sex- and age-specific way on the responses to auditory and contextual fear conditioning in adolescence and adulthood: (a) increased conditioned fear to the tone in males during adolescence but not during adulthood; (b) impaired extinction to the tone in adult males; and (c) reduced freezing responses to the context in adolescent females. Stress before puberty did not influence the corticosterone levels 30 minutes after an additional stressor given in adulthood. These results indicate that stress experienced prior to puberty can exert a sex-related differential impact on fear-related behaviors displayed by individuals during late adolescence and early adulthood.


SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A11-A11
Author(s):  
Joel Raymond ◽  
Nicholas Everett ◽  
Anand Gururajan ◽  
Michael Bowen

Abstract Introduction Oxytocin is a versatile hypothalamic neuropeptide involved in diverse neurobehavioural processes. Since oxytocin can elicit anxiolytic and serenic effects, one could hypothesise that oxytocin should prime the brain for sleep and promote hypnogenesis. However, based on the social salience hypothesis—that oxytocin promotes prosocial behaviour and directs attention toward social stimuli—one could also posit that oxytocin should promote wakefulness. At present, little research has comprehensively characterised the effect of oxytocin on sleep-wake behaviour and no explanation to reconcile these two seemingly competing hypotheses has been proposed. Methods This study investigated the effects of oxytocin on sleep-wake outcomes using radiotelemetry-based polysomnography in adult male and female Wistar rats. Oxytocin was administered via the intraperitoneal (IP; 0.1, 0.3 and 1 mg/kg) and intranasal (IN; 0.06, 1, 3 mg/kg) routes. Caffeine (IP and IN; 10 mg/kg) was also administered as a wake-promoting positive control. Additionally, pre-treatment with the oxytocin receptor (OTR) antagonist L-368,899 (IP; 5 mg/kg) and vasopressin 1a receptor (V1aR) antagonist SR49059 (IP; 1 mg/kg) followed by oxytocin (IP; 1 mg/kg) was conducted to determine which receptor(s) mediated sleep-wake effects of oxytocin. Results In both male and female rats, IP oxytocin produced dose-dependent effects on sleep-wake behaviour. Specifically, oxytocin initially promoted quiescent wakefulness (a restful but conscious state) at the cost of reducing both active wakefulness and sleep. Throughout the 1.5-hour period post-administration, oxytocin delayed REM sleep onset and reduced the proportion of both NREM and REM sleep. Conversely, IN oxytocin did not significantly alter any sleep-wake parameters at any dose tested. Caffeine demonstrated wake-promoting effects under both the IP and IN routes of administration. The involvement of OTR and V1aR binding in oxytocin-induced effects on sleep-wake outcomes will be discussed. Conclusion These findings appear to reconcile the two competing hypotheses: in rats, IP oxytocin appears to promote a state of quiescent wakefulness—one of calm and rest, but also of conscious responsivity to environmental stimuli. IN oxytocin demonstrated little to no effect on sleep-wake behaviour, which is a crucial finding given the escalating use of IN oxytocin as a therapeutic for conditions with comorbid disordered sleep. Support (if any) None.


2021 ◽  
pp. 100325
Author(s):  
Renata C.N. Marchette ◽  
Adriana Gregory-Flores ◽  
Brendan J. Tunstall ◽  
Erika R. Carlson ◽  
Shelley N. Jackson ◽  
...  

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.


1967 ◽  
Vol 56 (1) ◽  
pp. 165-176 ◽  
Author(s):  
Donald C. Johnson

ABSTRACT Ventral prostates in hypophysectomized male parabiotic partners of intact animals were used to compare the amount of plasma luteinizing hormone (LH) in males and females of various ages. Ovarian weight, histology, and augmentation with chorionic gonadotrophin, in hypophysectomized androgenized females were used to estimate plasma follicle stimulating hormone (FSH) activity in intact adult males and females. In young animals, up to 50 days of age, males apparently have the same amount of plasma LH as females, but older cyclic females produced significantly heavier prostates in their hypophysectomized male partners than did males. The results are consistent with the interpretation that cyclic surges of LH added to a tonic level produced an average value higher for females than males. In contrast, males of all ages and particularly adults, have a significantly greater amount of circulating FSH than females.


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