Behavioural pharmacology
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Although the gut and brain are separate organs, they communicate with each other via trillions of intestinal bacteria that collectively make up one's gut microbiome. Findings from both humans and animals support a critical role of gut microbes in regulating brain function, mood, and behavior. Gut bacteria influence neural circuits that are notably affected in addiction-related behaviors. ⋯ We present clinical and preclinical evidence supporting a bidirectional relationship between gut microbiota and opioid-related behaviors by highlighting the effects of opioid use on gut bacteria, and the effects of gut bacteria on behavioral responses to opioids. Further, we discuss possible mechanisms of this gut-brain communication influencing opioid use. By clarifying the relationship between the gut microbiome and opioid-related behaviors, we improve understanding on mechanisms mediating reward-, motivation-, and stress-related behaviors and disorders, which may contribute to the development of effective, targeted therapeutic interventions in opioid dependence and addiction.
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Behavioural pharmacology · Aug 2021
The selective 5-HT2A receptor agonist 25CN-NBOH does not affect reversal learning in mice.
Psychedelic 5-hydroxytryptamine 2A receptor (5-HT2AR) agonists are showing promise in the treatment of psychiatric disorders, such as treatment-resistant depression and anxiety. Human studies suggest that enhanced cognitive flexibility may contribute to their clinical efficacy. ⋯ No effects were observed on acquisition of the new stimulus-reward contingency, learning errors, or perseverative responses during reversal. Our results suggest that 25CN-NBOH does not affect reversal learning in the schedule used in this study.
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Behavioural pharmacology · Jun 2021
Effects of remifentanil/histamine mixtures in rats responding under a choice procedure.
Intravenous drug self-administration remains the 'gold standard' for assessing abuse liability. Failure of a drug to maintain self-administration might indicate the absence of positive reinforcing effects but might also indicate the presence of aversive effects. Sensitivity to aversive and punishing effects of drugs (as well as nondrug stimuli) might collectively determine the likelihood of use, abuse and relapse. ⋯ The effects of remifentanil/histamine mixtures generally were different from the constituent doses of histamine alone but not from remifentanil alone. A mixture containing 3.2 mg/kg/infusion histamine and either 0.001 or 0.0032 mg/kg/infusion remifentanil was not different from saline but was different from the effects of the constituent dose, insofar as choice increased compared with 3.2 mg/kg/infusion histamine alone and decreased compared with 0.001 or 0.0032 mg/kg/infusion remifentanil alone. Reinforcing doses of remifentanil combined with punishing doses of histamine can yield mixtures that are neither preferred nor avoided, offering 'proof-of-principle' for using drug mixtures to avoid adverse effects of opioid receptor agonists.
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Behavioural pharmacology · Oct 2016
ReviewCannabinoids and post-traumatic stress disorder: clinical and preclinical evidence for treatment and prevention.
There is substantial evidence from studies in humans and animal models for a role of the endocannabinoid system in the control of emotional states. Several studies have shown an association between exposure to trauma and substance use. Specifically, it has been shown that there is increased prevalence of cannabis use in post-traumatic stress disorder (PTSD) patients and vice versa. ⋯ There is a need for large-scale clinical trials examining the potential decrease in PTSD symptomatology with the use of cannabis. In animal models, there is a need for a better understanding of the mechanism of action and efficacy of cannabis. Nevertheless, the end result of the current clinical and preclinical data is that cannabinoid agents may offer therapeutic benefits for PTSD.
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Behavioural pharmacology · Apr 2016
Separate and combined effects of gabapentin and [INCREMENT]9-tetrahydrocannabinol in humans discriminating [INCREMENT]9-tetrahydrocannabinol.
The aim of the present study was to examine a potential mechanism of action of gabapentin to manage cannabis-use disorders by determining the interoceptive effects of gabapentin in cannabis users discriminating [INCREMENT]-tetrahydrocannabinol ([INCREMENT]-THC) using a pharmacologically selective drug-discrimination procedure. Eight cannabis users learned to discriminate 30 mg oral [INCREMENT]-THC from placebo and then received gabapentin (600 and 1200 mg), [INCREMENT]-THC (5, 15, and 30 mg), and placebo alone and in combination. ⋯ When administered concurrently, gabapentin shifted the discriminative-stimulus effects of [INCREMENT]-THC leftward/upward, and combinations of [INCREMENT]-THC and gabapentin generally produced larger effects on cannabinoid-sensitive outcomes relative to [INCREMENT]-THC alone. These results suggest that one mechanism by which gabapentin might facilitate cannabis abstinence is by producing effects that overlap with those of cannabinoids.