Dataset Information

High and Hyper: Fentanyl Induces Psychomotor Side-Effects in Healthy Pigs.

ABSTRACT: Analgesic effects of fentanyl have been investigated using behavior. The behavioral effects of fentanyl and possible serotonergic influence are largely unknown. We therefore investigated behavioral effects of fentanyl, with or without the serotonin antagonist ketanserin, in pigs. Fourteen mixed-breed pigs, weighing 17-25 kg were included in a randomised blinded prospective, balanced three-group study. Ten pigs received first 5 and then 10 µg/kg of fentanyl intravenously. Ketanserin at 1 mg/kg or saline was given intravenously as a third injection. Four control pigs received three injections of saline. Behavior was video-recorded. The distance moved was automatically measured by commercially available software, and behaviors manually scored in retrospect. Fentanyl inhibited resting and playing, and induced different repetitive behaviors. The mean (SD) distance moved in the control group and fentanyl group was 21.3 (13.0) and 57.8 (20.8) metres respectively (p < 0.05 for pairwise comparison). A stiff gait pattern was seen after fentanyl injection for median (range) 4.2 (2.8-5.1) minutes per 10 min, which was reduced to 0 (0-4) s after ketanserin administration. Conclusion: fentanyl-induced motor and behavioral effects, and serotonergic transmission may be involved in some of them. The psychomotor side effects of fentanyl could potentially interfere with post-operative pain evaluation in pigs.

SUBMITTER: Digranes N

PROVIDER: S-EPMC10215380 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

High and Hyper: Fentanyl Induces Psychomotor Side-Effects in Healthy Pigs.

Digranes Nora N Haga Henning Andreas HA Nordgreen Janicke J

Animals : an open access journal from MDPI 20230517 10

Analgesic effects of fentanyl have been investigated using behavior. The behavioral effects of fentanyl and possible serotonergic influence are largely unknown. We therefore investigated behavioral effects of fentanyl, with or without the serotonin antagonist ketanserin, in pigs. Fourteen mixed-breed pigs, weighing 17-25 kg were included in a randomised blinded prospective, balanced three-group study. Ten pigs received first 5 and then 10 µg/kg of fentanyl intravenously. Ketanserin at 1 mg/kg or ...[more]

PMID: 37238100

Similar Datasets

Project description:Background: Recently increased access to cannabis products in the United States has been associated with increased rates of driving after cannabis use. Although numerous studies indicate that cannabis impairs psychomotor and neurocognitive functions that can affect driving ability, the determination of cannabis-impaired driving risk is complicated by the extent to which frequent cannabis users develop tolerance to THC's subjective, cognitive, and psychomotor effects, and by the fact that there is no validated behavioral or biological marker of recent cannabis use or cannabis-related impairment. This study examined the psychomotor impairment-related effects experienced by frequent cannabis users in Colorado after naturalistic consumption of smoked cannabis, both immediately and 1 h postuse. Results were then validated in a smaller replication sample from Washington state. Methods: In the primary Colorado study, participants (n=70) used the DRUID® mobile app, a brief measure of psychomotor and cognitive domains that are sensitive to the effects of cannabis. First, participants used DRUID to establish a sober baseline impairment score. During a second appointment, they used DRUID at three time points: preuse, immediately after acutely using cannabis, and 1 h postuse. In the Washington replication sample, participants (n=39) used DRUID before acute cannabis consumption and then every half hour for 2.5 h. Results: In both studies, peak DRUID impairment effects were seen immediately after cannabis use, with recovery of performance at 1 h postuse. Specifically, significant quadratic effects of time emerged for both studies (Colorado study: (β=-0.935, SE=0.204, p<0.001); Washington study: β=3.0299, SE=1.3085, p<0.01). Domain-specific effects were tested in the larger Colorado study and were observed for reaction time within a complex divided attention task and a postural-stability balance task. Conclusions: These findings demonstrate that psychomotor impairment emerges immediately after acute cannabis use even in regular users, but decreases significantly 1 h postuse. These results underscore the potential utility of the DRUID app for assessing acute cannabis-related psychomotor impairment. Further research is needed to explore whether the DRUID app and/or the specific psychomotor functions it assesses might serve as a tool for measuring cannabis-related driving impairment. Clinical trials registration number for the Colorado Study: NCT03522103.

Project description:Obesity has become a serious public health problem. Although diet, surgery, and exercise are the primary treatments for obesity, these activities are often supplemented using appetite suppressants. A previous study reported that obesity specialists frequently prescribed a new drug combination for its treatment that includes phentermine (Phen; dopaminergic appetite suppressant), a serotonin (5-HT) precursor 5-hydroxytryptophan (5-HTP; an appetite suppressant that increases the 5-HT concentration), and carbidopa (CB; peripheral blocker of conversion of 5-HTP to 5-HT). Despite its widespread use, there is neither a preclinical study confirming the drug efficacy nor studies of its effects on the brain. To fill this gap, in rats for seven consecutive days, we administered Phen intraperitoneally at different doses either alone or in combination with a fixed dose of 5-HTP/CB. In a different group, we infused drugs via an intraperitoneal catheter while extracellular-recordings were performed in the nucleus accumbens shell (NAcSh), a brain region with dopamine-releasing effects that is involved in the action of appetite suppressants. We found that the triple-drug combination leads to greater weight-loss than each drug alone. Moreover, and as the treatment progresses, the triple drug combination partially reversed psychomotor side-effects induced by Phen. Electrophysiological results revealed that Phen alone evoked a net inhibitory imbalance in NAcSh population activity that correlated with the onset of psychomotor effects. In addition, and unlike the greater weight loss, the addition of 5-HTP/CB did not alter the Phen-evoked inhibitory imbalance in NAcSh responses. Subsequent experiments shed light on the underlying mechanism. That is the majority of NAcSh neurons modulated by 5-HTP/CB were suppressed by Phen. Notably, and despite acting via a different mechanism of action (DA for Phen vs. 5-HT for 5-HTP/CB), both drugs recruited largely overlapping NAcSh neuronal ensembles. These data suggest that the neural correlates of the greater weight loss could be located outside the NAcSh, in other brain circuits. Furthermore, we conclude that Phen + 5-HTP/CB is a potential treatment for overweight and obesity.

Dataset Information

High and Hyper: Fentanyl Induces Psychomotor Side-Effects in Healthy Pigs.

Publications

High and Hyper: Fentanyl Induces Psychomotor Side-Effects in Healthy Pigs.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets