134 Acute effects of methadone, buprenorphine or naltrexone on sleep-like parameters evaluated with actigraphy in male rhesus monkeys

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A54-A55
Author(s):  
Lais Berro ◽  
C Austin Zamarripa ◽  
Joseph Talley ◽  
Kevin Freeman ◽  
James Rowlett
Keyword(s):  
Rhesus Monkeys ◽  
Sleep Latency ◽  
Public Health Problem ◽  
Sleep Efficiency ◽  
Acute Administration ◽  
Acute Effects ◽  
Opioid Use ◽  
Sleep Impairment ◽  
Impaired Sleep ◽  
Male Rhesus

Abstract Introduction Opioid use disorder (OUD) is a significant public health problem, and it has been associated with the emergence of sleep disturbances. Effective treatment options for OUD exist, including medication-assisted therapy with methadone or buprenorphine. However, emerging evidence suggests that these treatments also may be associated with significant sleep impairment. The extent to which these effects are a result of the medication or an effect of chronic opioid use remains unknown. In the present study, we investigated the acute effects of methadone, buprenorphine or naltrexone in male rhesus monkeys in order to understand whether pharmacological treatment with these drugs per se would have deleterious effects on sleep. Methods Adult naïve male rhesus macaques (Macaca mulatta, n=5) maintained on a 12h/12h light/dark cycle were fitted with primate collars to which actigraphy monitors were attached. Actigraphy recording was conducted during baseline conditions and following acute injections of vehicle, methadone (0.03 – 1.0 mg/kg, i.m.), buprenorphine (0.01 – 1.0 mg/kg, i.m.) or naltrexone (0.03 – 1.0 mg/kg, i.m.) in the morning (10h, 4h after “lights on”) or in the evening (16:30h, 1.5h before “lights off”). Results Morning treatment with methadone or buprenorphine dose-dependently impaired sleep in rhesus monkeys, with at least one dose significantly increasing sleep latency and decreasing sleep efficiency. Evening treatment with methadone or buprenorphine also impaired sleep, with lower doses significantly inducing sleep alterations compared to morning treatments. The effects of buprenorphine on sleep was a biphasic function, with the highest doses not disrupting sleep. Treatment with naltrexone significantly improved sleep-like measures in rhesus monkeys, with evening treatments improving measures of both sleep latency and sleep efficiency. Conclusion Acute administration of methadone and buprenorphine induced marked sleep impairment in rhesus monkeys, even when the drugs were administered in the morning. Unexpectedly, acute administration of the opioid antagonist naltrexone significantly improved sleep-like measures. Our findings show that the currently available pharmacotherapies for OUD significantly affect sleep in naïve monkeys, and that opioid mechanisms yet to be determined may play a significant role in sleep-wake regulation. Support (if any) Supported by NIH grants DA049886 to L.F.B.; DA048586 to C.A.Z.; DA039167 to K.B.F.; DA011792, DA043204 and DA046778 to J.K.R..

Serum levels of testosterone, cortisol, prolactin and bioactive luteinizing hormone in adult male rhesus monkeys following cage-restraint or anaesthetizing with ketamine hydrochloride

1981 ◽  
Vol 97 (1) ◽  
pp. 118-124 ◽  
Author(s):  
C. P. Puri ◽  
V. Puri ◽  
T. C. Anand Kumar
Keyword(s):  
Luteinizing Hormone ◽  
Adult Male ◽  
Rhesus Monkeys ◽  
Serum Levels ◽  
Acute Effects ◽  
Experimental Procedure ◽  
Blood Samples ◽  
Ketamine Hydrochloride ◽  
Circulating Levels ◽  
Male Rhesus

Abstract. The present studies were carried out to characterize and compare the acute effects of cage-restraint or administration of a mild anaesthetic on serum levels of testosterone (T) cortisol (C), prolactin (Prl) and bioactive luteinizing hormone (LH) in adult male rhesus monkeys. Serum T levels declined progressively while C levels increased in the 3 sequential blood samples obtained at 20 min intervals from restrained monkeys. Prl and LH levels in the serum remained unaltered. Following single or multiple injections of ketamine hydrochloride (10 mg/kg) serum T levels did not decline progressively as seen in the blood samples obtained from the cage-restrained, conscious monkeys. Serum C and Prl levels showed a progressive rise following anaesthetization. LH levels were not affected by the anaesthetic. The findings reported here are of pertinent relevance to the evaluation of acute effects of any experimental procedure aimed at altering circulating levels of the hormones studied.

Effects of yoga, cognitive behavioral therapy, and a behavioral placebo on sleep: A nationwide multicenter phase III RCT in cancer survivors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 12017-12017
Author(s):  
Po-Ju Lin ◽  
Charles E. Heckler ◽  
Eva Culakova ◽  
Huiwen Xu ◽  
Richard Francis Dunne ◽  
...  
Keyword(s):  
Cognitive Behavioral Therapy ◽  
Cancer Survivors ◽  
Sleep Duration ◽  
Sleep Latency ◽  
Behavioral Therapy ◽  
Sleep Efficiency ◽  
Phase Iii ◽  
Post Intervention ◽  
Multicenter Phase ◽  
Impaired Sleep

12017 Background: Patients commonly experience impaired sleep throughout cancer treatment and for years into survivorship. Impaired sleep may mediate other cancer-related symptoms and can lead to the inability to complete daily activities and lower quality of life. More effective non-pharmacological treatment options for impaired sleep are needed. We conducted a nationwide, multicenter, phase III randomized controlled trial (RCT) comparing the effects of yoga (Yoga for Cancer Survivors; YOCAS), cognitive behavioral therapy for insomnia (CBT-I), and a behavioral placebo on impaired sleep in cancer survivors. Methods: This RCT was conducted via the URCC NCORP Research Base. Participants were cancer survivors 2-60 months post-treatment with insomnia. They were randomized to 1) YOCAS (75-min session biweekly for 4 wks), 2) CBT-I (90-min session weekly for 8 wks), and 3) behavioral placebo (survivorship health education per ASCO guidelines; 75-min session biweekly for 4 wks). Sleep efficiency, sleep duration, wake after sleep onset (WASO), and sleep latency were assessed via actigraphy at baseline and post-intervention. Actigraphs were worn on the non-dominant wrist 24 hours a day for 7 days. Linear mixed models were used to assess intervention effects on sleep outcomes. Results: 740 survivors were enrolled (93% female, mean age 56±11 years, 73% breast cancer). Results revealed significant group differences among survivors in the 3 arms in sleep efficiency, sleep duration, and WASO (all p<0.05), but not in sleep latency (p>0.05). YOCAS and CBT-I subjects maintained sleep efficiency (mean change= -0.8% and -0.03%, respectively, all p>0.05) while behavioral placebo subjects significantly reduced sleep efficiency (mean change= -3.4%, p<0.01). When controlling for baseline, YOCAS and CBT-I subjects demonstrated better sleep efficiency compared to behavioral placebo subjects at post-intervention (all p<0.05). YOCAS subjects also maintained sleep duration (mean change= -3.5 minutes, p>0.05) while CBT-I and behavioral placebo subjects significantly reduced sleep duration (mean change= -20.3 minutes and -26.6 minutes, respectively, all p<0.01). When controlling for baseline, YOCAS subjects demonstrated longer sleep duration compared to CBT-I and behavioral placebo subjects at post-intervention (all p<0.05). There were no significant within-group changes in WASO over time in the 3 arms. When controlling for baseline, CBT-I subjects demonstrated a trend toward lower WASO compared to YOCAS (p=0.07) and behavioral placebo (p=0.05) subjects at post-intervention. Conclusions: Both YOCAS and CBT-I maintained sleep efficiency and/or sleep duration among cancer survivors. Oncologists should consider prescribing yoga and CBT-I for treating impaired sleep in cancer survivors. Funding: NCI UG1CA189961, R01CA181064, T32CA102618. Clinical trial information: NCT02613364.

Acute Effects of Nalmefene on LH, Prolactin, and Testosterone in Male Rhesus Monkeys

2000 ◽  
Vol 66 (2) ◽  
pp. 275-283 ◽  
Author(s):  
Nancy K Mello ◽  
Jack H Mendelson ◽  
Maureen Kelly
Keyword(s):  
Rhesus Monkeys ◽  
Acute Effects ◽  
Male Rhesus

Evaluation of hippocampus in rhesus monkeys after chronic (1-year) inhalation exposure to marijuana: I. Electron microscopy

1990 ◽  
Vol 48 (3) ◽  
pp. 398-399
Author(s):  
A.M. Andrews ◽  
S.W. Wilson ◽  
A.C. Scallet ◽  
S.F. Ali ◽  
J. Bailey ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
Rhesus Monkeys ◽  
Low Dose ◽  
Inhalation Exposure ◽  
Synaptic Cleft ◽  
High Dose ◽  
Withdrawal Time ◽  
Treatment Groups ◽  
Ultrastructural Evidence ◽  
Male Rhesus

Exposure of rhesus monkeys (Macaca mulatta) to marijuana via inhalation or to intravenous delta-9-tetrahydrocannabinol (THC), reportedly caused ultrastructural evidence of increased synaptic width. Chronic marijuana smoke in a single rhesus monkey examined after a six month withdrawal time caused ultrastructure changes in the septal, hippocampal and amygdala regions; the synaptic cleft was widened, electron opaque material was found in the cleft and in the pre- and postsynaptic regions, with some clumping of the synaptic vesicles. The objective of our study was to assess neuropathological alterations produced by chronic inhalation of marijuana smoke.Nineteen male rhesus monkeys, 3-5 years of age and weighing 3-8 kg, were divided into four treatment groups: a) sham control, b) placebo smoke (7 days/ week) c) low dose marijuana (2 times/week with 5 days/week sham) and d) high dose marijuana (7 times/week). A smoke exposure consisted of smoke from one cigarette (2.6% THC) burned down to 10 mm butt length. Smoke was administered via smoke generator (ADL II, Arthur D. Little, Inc. Cambridge, MA) and nose-mouth only masks (local production) equipped with one-way valves.

Experimental delayed radiation necrosis of the brain

1979 ◽  
Vol 51 (5) ◽  
pp. 587-596 ◽  
Author(s):  
Albert N. Martins ◽  
Ralph E. Severance ◽  
James M. Henry ◽  
Thomas F. Doyle
Keyword(s):  
Rhesus Monkeys ◽  
Radiation Necrosis ◽  
Clinical Signs ◽  
Control Group ◽  
Content Type ◽  
Brain Irradiation ◽  
Primate Brain ◽  
High Doses ◽  
The Brain ◽  
Male Rhesus

✓ The authors have designed an experiment to detect a hitherto unrecognized interaction between high doses of the glucocorticoid, dexamethasone, and brain irradiation. Eighteen juvenile male rhesus monkeys received 1800 rads to the whole brain in 8.5 minutes. For 1½ days before and 10½ days after the irradiation, nine animals received approximately 2.9 mg/kg/day of dexamethasone intramuscularly in addition to irradiation, while the remaining nine animals served as the control group and received saline. All animals eventually developed a progressive neurological syndrome, and died of delayed radiation necrosis of the brain. The two groups were compared with regard to latency to onset of clinical signs, survival time, and number, distribution, and location of lesions of radionecrosis. Large doses of dexamethasone did not alter the susceptibility of the primate brain to delayed radiation necrosis. Detailed morphological study of the radionecrotic lesions supports the hypothesis that most, if not all, of the lesions develop as the consequence of injury to blood vessels.

Acute effects of marijuana smoke on complex operant behavior in rhesus monkeys

Life Sciences ◽  
1989 ◽  
Vol 45 (6) ◽  
pp. 465-475 ◽  
Author(s):  
Gene E. Schulze ◽  
D.E. McMillan ◽  
John R. Bailey ◽  
Andrew C. Scallet ◽  
Syed F. Ali ◽  
...  
Keyword(s):  
Operant Behavior ◽  
Rhesus Monkeys ◽  
Acute Effects

Pituitary response to LRH and TRH stimulation and peripheral steroid hormones in conscious and anaesthetized adult male rhesus monkeys (Macaca mulatta)

1980 ◽  
Vol 93 (3) ◽  
pp. 287-293 ◽  
Author(s):  
E. Jean Wickings ◽  
E. Nieschlag
Keyword(s):  
Adult Male ◽  
Rhesus Monkeys ◽  
Serum Testosterone ◽  
Fold Increase ◽  
Serum Cortisol ◽  
Serum Levels ◽  
Biologically Active ◽  
Similar Response ◽  
Response Curves ◽  
Male Rhesus

Abstract. Adult male rhesus monkeys are aggressive animals and very difficult to handle. Hence experimental manipulations necessarily involve the use of restraint procedures, either chemical or physical, which may influence endocrine functions. Therefore, the effects of ketamine anaesthesia on basal hormone levels and on the pituitary response to LRH and TRH were investigated in 4 adult male rhesus monkeys. Values were compared to those obtained from the same animals restrained in primate chairs for approximately 48 h, a procedure to which they had been accustomed to over the preceding 6 months. Serum cortisol levels under anaesthesia were at all times lower than in conscious monkeys, but increased after 2 h to values twice as high as measured initially. Serum testosterone concentrations were not significantly different on the two occasions, but levels under anaesthesia were slightly higher initially than in the conscious monkeys, and decreased gradually over the 3 h test period. Initial prolactin levels were lower in the anaesthetized monkeys, and increased 2–3-fold after 90 min; values at 3 h were not significantly different from those in conscious monkeys. Intravenous TRH elicited a similar response in prolactin on both occasions, maximum values occurring after 15–30 min and returning to basal levels after 3 h. The maximum values attained and the area under the response curves were higher under anaesthesia. LRH stimulation resulted in a 15- and 30-fold increase in serum levels of biologically active LH, with and without anaesthesia, respectively. Basal levels were not significantly different on the two occasions. The area under the LH response curve was higher in 3 of the 4 monkeys without anaesthesia. The extent to which results in conscious monkeys are affected by stress is difficult to assess. Since neither handling technique allows for the collection of 'true' basal data, it is paramount to standardize and define the conditions under which experiments, and even routine blood sampling, are performed in male rhesus monkeys.

The effects of heroin on prolactin levels in male rhesus monkeys: use of cumulative-dosing procedures

2002 ◽  
Vol 27 (3) ◽  
pp. 319-336 ◽  
Author(s):  
Carrie A. Bowen ◽  
S. Stevens Negus ◽  
Maureen Kelly ◽  
Nancy K. Mello
Keyword(s):  
Rhesus Monkeys ◽  
Male Rhesus

A review of the evidence to explain pharmacological basis of injection (ab)use of buprenorphine–naloxone tablets

2021 ◽  
Vol 17 (7) ◽  
pp. 141-152
Author(s):  
Tamoud Modak, MD, DM ◽  
Siddharth Sarkar, MD, MRCPsych ◽  
Yatan Pal Singh Balhara, MD
Keyword(s):  
Public Health Problem ◽  
Opioid Use Disorder ◽  
Critical Examination ◽  
Evidence Based ◽  
Major Public Health Problem ◽  
Opioid Use ◽  
Evidence Based Treatment ◽  
Opioid Replacement Therapy ◽  
Pharmacological Basis

Opioid use disorder is a major public health problem, and opioid replacement therapy with buprenorphine (BPN) is a clinically effective and evidence-based treatment for it. To deter misuse of the tablet through the injecting route, BPN coformulated with naloxone (BNX) in 4:1 ratio is available in many countries. Despite this, significant diversion and injecting use of the BNX combination has been reported from across the world. In this article, the pharmacological properties of BPN and BNX and the evidence for their diversion are reviewed. Also, a critical examination is made of the evidence supporting the role of naloxone in reducing the agonist effects of BPN when used through the injecting route. Based on this evidence, a hypothesis explaining the continued diversion of BNX has been proposed.

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