Dataset Information

Behavioral Characterization of the Effects of Cannabis Smoke and Anandamide in Rats.

ABSTRACT: Cannabis is the most widely used illicit drug in the world. Delta-9-tetrahydrocannabinol (?9-THC) is the main psychoactive component of cannabis and its effects have been well-studied. However, cannabis contains many other cannabinoids that affect brain function. Therefore, these studies investigated the effect of cannabis smoke exposure on locomotor activity, rearing, anxiety-like behavior, and the development of dependence in rats. It was also investigated if cannabis smoke exposure leads to tolerance to the locomotor-suppressant effects of the endogenous cannabinoid anandamide. Cannabis smoke was generated by burning 5.7% ?9-THC cannabis cigarettes in a smoking machine. The effect of cannabis smoke on the behavior of rats in a small and large open field and an elevated plus maze was evaluated. Cannabis smoke exposure induced a brief increase in locomotor activity followed by a prolonged decrease in locomotor activity and rearing in the 30-min small open field test. The cannabinoid receptor type 1 (CB1) receptor antagonist rimonabant increased locomotor activity and prevented the smoke-induced decrease in rearing. Smoke exposure also increased locomotor activity in the 5-min large open field test and the elevated plus maze test. The smoke exposed rats spent more time in the center zone of the large open field, which is indicative of a decrease in anxiety-like behavior. A high dose of anandamide decreased locomotor activity and rearing in the small open field and this was not prevented by rimonabant or pre-exposure to cannabis smoke. Serum ?9-THC levels were 225 ng/ml after smoke exposure, which is similar to levels in humans after smoking cannabis. Exposure to cannabis smoke led to dependence as indicated by more rimonabant-precipitated somatic withdrawal signs in the cannabis smoke exposed rats than in the air-control rats. In conclusion, chronic cannabis smoke exposure in rats leads to clinically relevant ?9-THC levels, dependence, and has a biphasic effect on locomotor activity.

SUBMITTER: Bruijnzeel AW

PROVIDER: S-EPMC4827836 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Behavioral Characterization of the Effects of Cannabis Smoke and Anandamide in Rats.

Bruijnzeel Adriaan W AW Qi Xiaoli X Guzhva Lidia V LV Wall Shannon S Deng Jie V JV Gold Mark S MS Febo Marcelo M Setlow Barry B

PloS one 20160411 4

Cannabis is the most widely used illicit drug in the world. Delta-9-tetrahydrocannabinol (Δ9-THC) is the main psychoactive component of cannabis and its effects have been well-studied. However, cannabis contains many other cannabinoids that affect brain function. Therefore, these studies investigated the effect of cannabis smoke exposure on locomotor activity, rearing, anxiety-like behavior, and the development of dependence in rats. It was also investigated if cannabis smoke exposure leads to t ...[more]

PMID: 27065006

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Project description:Alzheimer's disease (AD) is characterized by multiple cognitive deficits including memory and sensorimotor gating impairments as a result of neuronal and synaptic loss. The endocannabinoid system plays an important role in these deficits but little is known about its influence on the molecular mechanism regarding phosphorylated tau (p-tau) protein accumulation - one of the hallmarks of AD -, and on the density of synaptic proteins. Thus, the aim of this study was to investigate the preventive effects of anandamide (N-arachidonoylethanolamine, AEA) on multiple cognitive deficits and on the levels of synaptic proteins (syntaxin 1, synaptophysin and synaptosomal-associated protein, SNAP-25), cannabinoid receptor type 1 (CB1) and molecules related to p-tau degradation machinery (heat shock protein 70, HSP70), and Bcl2-associated athanogene (BAG2) in an AD-like sporadic dementia model in rats using intracerebroventricular (icv) injection of streptozotocin (STZ). Our hypothesis is that AEA could interact with HSP70, modulating the level of p-tau and synaptic proteins, preventing STZ-induced cognitive impairments. Thirty days after receiving bilateral icv injections of AEA or STZ or both, the cognitive performance of adult male Wistar rats was evaluated in the object recognition test, by the escape latency in the elevated plus maze (EPM), by the tone and context fear conditioning as well as in prepulse inhibition tests. Subsequently, the animals were euthanized and their brains were removed for histological analysis or for protein quantification by Western Blotting. The behavioral results showed that STZ impaired recognition, plus maze and tone fear memories but did not affect contextual fear memory and prepulse inhibition. Moreover, AEA prevented recognition and non-associative emotional memory impairments induced by STZ, but did not influence tone fear conditioning. STZ increased the brain ventricular area and this enlargement was prevented by AEA. Additionally, STZ reduced the levels of p-tau (Ser199/202) and increased p-tau (Ser396), although AEA did not affect these alterations. HSP70 was found diminished only by STZ, while BAG2 levels were decreased by STZ and AEA. Synaptophysin, syntaxin and CB1 receptor levels were reduced by STZ, but only syntaxin was recovered by AEA. Altogether, albeit AEA failed to modify some AD-like neurochemical alterations, it partially prevented STZ-induced cognitive impairments, changes in synaptic markers and ventricle enlargement. This study showed, for the first time, that the administration of an endocannabinoid can prevent AD-like effects induced by STZ, boosting further investigations about the modulation of endocannabinoid levels as a therapeutic approach for AD.

Project description:ObjectiveBehavioral economics suggest that cannabis reinforcing value (cannabis demand) may be influenced by external, contextual factors such as the social reward that might accompany cannabis use and the presence of opportunity costs (e.g., a next-day responsibility that cannabis use might adversely impact). The present study examined the effect of social context and opportunity cost on cannabis demand and explored whether relations were moderated by cannabis use severity.MethodAdults with past-week cannabis use recruited from Amazon's Mechanical Turk (N = 310; 53.5% female, 79.4% White) completed four purchase tasks, in which participants reported how much cannabis they would purchase across escalating prices, to index cannabis demand under varying contexts: (a) solitary, typical responsibilities; (b) social, typical responsibilities; (c) solitary, substantial responsibilities; and (d) social, substantial responsibilities.ResultsThe presence of peers significantly increased demand intensity (consumption at zero price) and Omax (maximum expenditure) relative to the solitary conditions. Substantial responsibilities significantly decreased intensity, breakpoint (price at which consumption is fully suppressed), and Pmax (price at which maximum expenditure occurs) and increased elasticity (greater price sensitivity). Demand was most inelastic in the social, typical responsibilities condition relative to other conditions. Cannabis use severity was associated with less elastic demand in the solitary, typical responsibilities condition. Those with higher cannabis use severity reported larger differences in demand intensity and Omax between solitary and social conditions, and in demand elasticity between typical and substantial responsibility conditions.ConclusionsResults are consistent with previous research illustrating social and opportunity costs as determinants of cannabis use behavior. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

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Behavioral Characterization of the Effects of Cannabis Smoke and Anandamide in Rats.

Publications

Behavioral Characterization of the Effects of Cannabis Smoke and Anandamide in Rats.

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