Behaviorally active doses of the CB1 receptor antagonist SR 141716A increase brain serotonin and dopamine levels and turnover

Darmani, Nissar A.; Janoyan, Jano J.; Kumar, Natasha N.; Crim, Jennifer L.

doi:10.1016/s0091-3057(03)00150-3

Cited by 92 publications

(69 citation statements)

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“…Administration of a D 2 agonist increased striatal levels of the endogenous endocannabinoid anandamide in vivo [72], and D 2 antagonist administration may decrease anandamide levels, leading to compensatory upregulation of CB 1 receptors. Furthermore, CB 1 receptors have been demonstrated to regulate 5-HT 2A/C -mediated behaviors, possibly through the regulation of serotonin [73,74], but whether serotonin exerts any affects on CB 1 receptor regulation remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

“…CB 1 receptors are present on serotonergic and dopaminergic neurons both in soma and synaptic terminals and modulate neurotransmission [75]. Administration of the CB 1 receptor antagonist SR141716A increased the levels and turnover of serotonin and dopamine in the forebrain, indicating inhibitory control of these monoamines by CB 1 receptors [74]. In animals, administration of amphetamine causes behavioral activation, such as increased locomotor activity, which has been used as a model to predict antipsychotic efficacy [76].…”

Section: Discussionmentioning

confidence: 99%

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Risperidone Treatment Increases CB<sub>1</sub> Receptor Binding in Rat Brain

et al. 2009

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Background/Aims: Body weight gain is a common side effect of treatment with antipsychotics, but the mechanisms underlying this weight gain are unknown. Several factors may be involved in antipsychotic-induced body weight gain including the cannabinoid receptor 1 (CB₁), the serotonin receptor 2C, the ghrelin receptor, neuropeptide Y, adiponectin and proopiomelanocortin. We investigated whether the expression of these factors was affected in rats chronically treated with the antipsychotic risperidone. Methods: Male Sprague-Dawley rats were treated with risperidone (1.0 mg/kg/day) or vehicle (20% hydroxypropyl β-cyclodextrin) for 28 days. Expression of the aforementioned factors were examined together with plasma prolactin and ghrelin levels. Results: No difference in body weight gained during treatment was observed between risperidone and vehicle treated rats, but plasma risperidone levels positively correlated with visceral fat mass. Risperidone treatment increased CB₁ receptor binding in the arcuate nucleus (40%), hippocampus (25–30%) and amygdala (35%) without concurrent alterations in the CB₁ receptor mRNA. Risperidone treatment increased adiponectin mRNA. Conclusion: The present study showed that risperidone treatment altered CB₁ receptor binding in the rat brain. Risperidone-induced adiposity and metabolic dysfunction in the clinic may be explained by increased CB₁ receptor density in brain regions involved in appetite and regulation of metabolic function.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Risperidone Treatment Increases CB<sub>1</sub> Receptor Binding in Rat Brain

et al. 2009

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“…54 Since the head-twitch behavior induced by psychedelic drugs is either attenuated or induced by CB 1 receptor agonists (e.g., tetrahydrocannabinol, THC) and antagonists, respectively, together these findings point toward a close functional crosstalk between 5-HT 2A and CB 1 receptors. 51,52,55 The head-twitch behavioral response induced by psychedelic 5-HT 2A agonists is decreased in knockout mice for the metabotropic glutamate 2 (mGlu2) receptor. 56 This glutamate receptor has been shown to be expressed in close molecular proximity with the 5-HT 2A receptor in tissue culture and mouse frontal cortex.…”

Section: Acs Chemical Neurosciencementioning

confidence: 99%

Animal Models of Serotonergic Psychedelics

Hanks

González-Maeso

2012

ACS Chem. Neurosci.

130

112

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The serotonin 5-HT 2A receptor is the major target of psychedelic drugs such as lysergic acid diethylamide (LSD), mescaline, and psilocybin. Serotonergic psychedelics induce profound effects on cognition, emotion, and sensory processing that often seem uniquely human. This raises questions about the validity of animal models of psychedelic drug action. Nonetheless, recent findings suggest behavioral abnormalities elicited by psychedelics in rodents that predict such effects in humans. Here we review the behavioral effects induced by psychedelic drugs in rodent models, discuss the translational potential of these findings, and define areas where further research is needed to better understand the molecular mechanisms and neuronal circuits underlying their neuropsychological effects.KEYWORDS: Psychedelic, hallucinogenic, schizophrenia, psychosis, serotonin 5-HT 2A receptor, G protein-coupled receptor (GPCR), lysergic acid diethylamide (LSD), mouse behavior models E lucidating the mechanisms by which psychedelics induce their unique neuropsychological effects has important implications for a better understanding of behavioral processes such as cognition, perception, emotion, and sense of self. 1−5 The term psychedelic was coined in 1957 by the British psychiatrist Humphry Osmond to describe the effects of psychoactive drugs such as psilocybin, mescaline, and lysergic acid diethylamide (LSD). 6 These drugs belong to a larger group of substances known as hallucinogens, which also includes dissociatives (e.g., ketamine and phencyclidine), and deliriants (e.g., scopolamine and atropine), as well as compounds such as salvinorin A. Psychedelics all behave as agonists or partial agonists at the serotonin 5-HT 2A receptor, whereas dissociatives and deliriants have been identified as noncompetitive NMDA receptor antagonists, and competitive muscarinic receptor antagonists, respectively. Salvinorin A is a potent κ-opioid receptor agonist. 7−12 Although all of these hallucinogenic drugs profoundly alter perception, according to the Hallucinogen Rating Scale (HRS) and the Five-Dimensional Altered States of Consciousness (5D-ASC) rating scale, there are also features that are unique to each of these groups. 13−15 Research using behavioral and cognitive tasks indicates that different groups of hallucinogens induce overlapping, yet distinct sets of changes in sensory processing. Recent findings regarding the molecular mechanism of action of psychedelic and other hallucinogenic drugs have been reviewed elsewhere. 7,8,11,16−24 In this review, we will discuss the effects of psychedelics in a range of animal behavioral assays, and their utility as preclinical models of the effects of these drugs in humans. ■ MODELING PSYCHOSIS IN ANIMALSModeling in rodents the neuropsychological effects induced by psychedelic drugs remains controversial. The above-mentioned psychometric rating scales HRS and 5D-ASC measure aspects of subjective experience such as "oceanic boundlessness", "dread of ego dissolution", and "spiritual expe...

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“…Furthermore, Sallan et al (1975) found that the active component of C. sativa have antiemetic property, which reside in its ability to stimulate cannabinoid receptor type 1 (CB 1 ) (Darmani, 2001a). Presynaptically, located CB 1 receptors stimulation have inhibitory effect on neurotransmitter (serotonin, norepinephrine, dopamine, and acetylcholine) release (Darmani et al, 2003) and this inhibition of ongoing contractile transmitter release in the enteric nervous system leads to depression of gastrointestinal (GIT) motility (Pertwee, 2001a). Moreover, cisplatin also dose dependently inhibits gastric emptying in rats and mice (Sharma and Gupta, 1998).…”

Section: Introductionmentioning

confidence: 99%