Involvement of 5-hydroxytryptamine neuronal system in Δ9-tetrahydrocannabinol-induced impairment of spatial memory

Egashira, Nobuaki; Mishima, Kenichi; Katsurabayashi, Shutaro; Yoshitake, T.; Matsumoto, Yoshiaki; Ishida, Junichi; Yamaguchi, Masatoshi; Iwasaki, Katsunori; Fujiwara, Michihiro

doi:10.1016/s0014-2999(02)01755-7

Cited by 78 publications

(43 citation statements)

References 55 publications

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“…We previously reported that D 9 -THC (6 mg / kg, i.p. ), which impairs spatial memory, markedly reduced release of ACh and 5-HT in the dorsal or ventral hippocampus (6,23). We also reported that cholinesterase inhibitors and 5-HT agonists improved D 9 -THC-induced impairment of spatial memory (6,23).…”

Section: +mentioning

confidence: 60%

New Perspectives in the Studies on Endocannabinoid and Cannabis: Abnormal Behaviors Associate With CB1 Cannabinoid Receptor and Development of Therapeutic Application

Fujiwara

Egashira

2004

J Pharmacol Sci

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Abstract. D 9-Tetrahydrocannabinol (D 9 -THC), the major psychoactive component of marijuana, induces catalepsy-like immobilization and impairment of spatial memory in rats. D 9 -THC also induces aggressive behavior in isolated housing stress. These abnormal behaviors could be counteracted by SR141716A, a CB 1 cannabinoid receptor antagonist. Also D 9 -THC inhibited release of glutamate in the dorsal hippocampus, but this inhibition could be antagonized by SR141716A in an in vivo microdialysis study. Moreover, NMDA and AMPA-type glutamate receptor enhancers improved the D 9 -THC-induced impairment of spatial memory. On the other hand, D 9-THC markedly inhibited the neurodegeneration in experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis and reduced the elevated glutamate level of cerebrospinal fluid induced by EAE. These therapeutic effects on EAE were reversed by SR141716A. Taken together, our results demonstrate that the inhibition of glutamate release via activation of the CB 1 -cannabinoid receptor is one mechanism involved in D 9-THC-induced impairment of spatial memory, and the therapeutic effect of D 9 -THC on EAE, and a D 9 -THC analog might provide an effective treatment for psychosis and neurodegenerative diseases.

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Section: +mentioning

confidence: 60%

New Perspectives in the Studies on Endocannabinoid and Cannabis: Abnormal Behaviors Associate With CB1 Cannabinoid Receptor and Development of Therapeutic Application

Fujiwara

Egashira

2004

J Pharmacol Sci

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“…On the other hand, we previously reported that DOI attenuated the THC-induced impairment of spatial memory observed in rats in the eight-arm radial maze (13). Moreover, THC, CB 1 -receptor agonists and an endogenous cannabinoid inhibited the DOI-induced 5-HT 2A -receptor-mediated behaviors in mice (14,15).…”

mentioning

confidence: 81%

2,5-Dimethoxy-4-iodoamphetamine (DOI) Inhibits Δ9-Tetrahydrocannabinol-Induced Catalepsy-Like Immobilization in Mice

Egashira¹,

Koushi²,

Mishima³

et al. 2007

J Pharmacol Sci

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Abstract. The effect of the serotonin 5-HT 2A/ 2C -receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) on ∆ 9 -tetrahydrocannabinol (THC)-induced catalepsy-like immobilization was studied in mice. DOI (0.3 and 1 mg / kg, i.p.) significantly inhibited the catalepsy-like immobilization induced by THC (10 mg / kg, i.p.). In contrast, the selective 5-HT 2C -receptor agonist 8,9-dichloro-2,3,4,4a-tetrahydro-1H-pyrazino[1,2-a]quinoxalin-5(6H)-one (WAY 161503) had no effect on this catalepsy-like immobilization. Moreover, the 5-HT 2A -receptor antagonist ketanserin (0.3 mg / kg, i.p.) reversed the inhibition of THC-induced catalepsy-like immobilization caused by DOI (1 mg/kg), whereas the selective 5-HT 2C -receptor antagonist 6-chloro-2,3-dihydro-5-methyl-N-[6-(2-methyl-3-pyridinyl)oxyl]-3-pyridinyl]-1H-indole-1-carboxyamide (SB 242084) did not affect this inhibitory effect of DOI. On the other hand, ketanserin (0.3 and 1 mg / kg, i.p.) enhanced the catalepsy-like immobilization induced by THC (6 mg / kg, i.p.). Thus, on the basis of these results, it appears that 5-HT 2A -receptor mechanisms might be responsible for the inhibitory effect of DOI on THC-induced catalepsy-like immobilization.

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“…Acutely, THC has been reported to suppress 5-HT neurotransmission in the hippocampus by inhibiting 5-HT release. 276 Long-term cannabinoid administration can affect the response to a single challenge of a 5-HT 1A and 5-HT 2A receptor agonist. Twelve days of pretreatment with a cannabinoid receptor agonist resulted in an apparent upregulation of 5-HT 2A receptor activity and a downregulation of 5-HT 1A receptor activity.…”

Section: 4-methylenedioxymethamphetamine (Mdma)mentioning

confidence: 99%

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

et al. 2006

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In recent years, the term serotonergic vulnerability (SV) has been used in scientific literature, but so far it has not been explicitly defined. This review article attempts to elucidate the SV concept. SV can be defined as increased sensitivity to natural or experimental alterations of the serotonergic (5-HTergic) system. Several factors that may disrupt the 5-HTergic system and hence contribute to SV are discussed, including genetic factors, female gender, personality characteristics, several types of stress and drug use. It is explained that SV can be demonstrated by means of manipulations of the 5-HTergic system, such as 5-HT challenges or acute tryptophan depletion (ATD). Results of 5-HT challenge studies and ATD studies are discussed in terms of their implications for the concept of SV. A model is proposed in which a combination of various factors that may compromise 5-HT functioning in one person can result in depression or other 5-HT-related pathology. By manipulating 5-HT levels, in particular with ATD, vulnerable subjects may be identified before pathology initiates, providing the opportunity to take preventive action. Although it is not likely that this model applies to all cases of depression, or is able to identify all vulnerable subjects, the strength of the model is that it may enable identification of vulnerable subjects before the 5-HT related pathology occurs. Molecular Psychiatry ( Keywords: serotonin; mood disorders; stress; genetics; sex; tryptophan Involvement of serotonin in depressionMood disorders are one of the most prevalent forms of mental illness. 1 According to the DSM-IV, the lifetime risk for major depressive disorder is between 10 and 25% for women and between 5 and 12% for men. 2 Depression has been studied intensively during the last few decades, but the psychological and neurobiological determinants of depression have not yet been precisely defined. Although several factors are known to contribute to the etiology of depression, it is not clear how these factors cause depression, and why some subjects become depressed while others remain unaffected. In terms of biological factors in the etiology of depression, there are several hypotheses. These include neurotransmitter dysfunctions (serotonin, 5-HT; dopamine, DA; norepinephrine, NE); dysregulations in hypothalamic-pituitary-adrenal (HPA) axis activity; and immune system imbalance. The aim of this article is not to discuss all of these hypotheses in detail, but to evaluate the role that serotonin may play within these hypothesized mechanisms.It is widely accepted that diminished serotonergic (5-HTergic) function is involved in the onset and course of depression. 3,4 The 5-HTergic system is a large and complex system. Although nearly all cell bodies of 5-HTergic neurons are located in the raphe nuclei in the brain stem, the axons of these neurons innervate almost the entire brain. The actions of 5-HT are mediated by 16 types and subtypes of receptors. 5 As the 5-HTergic system is assumed to be a modulatory system, the exact func...

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Involvement of 5-hydroxytryptamine neuronal system in Δ9-tetrahydrocannabinol-induced impairment of spatial memory

Cited by 78 publications

References 55 publications

New Perspectives in the Studies on Endocannabinoid and Cannabis: Abnormal Behaviors Associate With CB1 Cannabinoid Receptor and Development of Therapeutic Application

New Perspectives in the Studies on Endocannabinoid and Cannabis: Abnormal Behaviors Associate With CB1 Cannabinoid Receptor and Development of Therapeutic Application

2,5-Dimethoxy-4-iodoamphetamine (DOI) Inhibits Δ9-Tetrahydrocannabinol-Induced Catalepsy-Like Immobilization in Mice

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

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