The central neuropharmcology of psychotropic cannabinoids

Pertwee, Roger G.

doi:10.1016/0163-7258(88)90106-4

Cited by 160 publications

(92 citation statements)

References 193 publications

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“…Cannabinoids are the primary psychoactive constituents of marijuana that have profound effects on pain perception, neural convulsions, memory and motor coordination [1,2]. Their effects are most commonly mediated by the CB1 cannabinoid receptor (CB1R), which is highly expressed in a variety of brain regions, including the hypothalamus [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

L-type channel inhibition by CB1 cannabinoid receptors is mediated by PTX-sensitive G proteins and cAMP/PKA in GT1-7 hypothalamic neurons

et al. 2009

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a b s t r a c tUsing immortalized hypothalamic GT1-7 neurons, which express the CB1 cannabinoid receptor (CB1R) and three Ca 2+ channel types (T, R and L), we found that the CB1R agonist WIN 55,212-2 inhibited the voltage-gated Ca 2+ currents by about 35%. The inhibition by WIN 55,212-2 (10 M) was reversible and prevented by nifedipine (3 M), suggesting a selective action on L-type Ca 2+ channels (LTCCs). WIN 55,212-2 action exhibited all the features of voltage-independent Ca 2+ channel modulation: (1) no changes of the activation kinetics, (2) equal depressive action at all potentials and (3) no facilitation following strong prepulses. At variance with WIN 55,212-2, the CB1R inverse agonist AM-251 (10 M) caused 20% increase of Ca 2+ currents. The inhibition of LTCCs by WIN 55,212-2 was prevented by overnight PTX-incubation and by intracellular perfusion with GDP-␤-S. The latter caused also a 20% Ca 2+ current up-regulation. WIN 55,212-2 action was also prevented by application of the PKA-blocker H89 or by loading the neurons with 8-CPT-cAMP. Our results suggest that LTCCs in GT1-7 neurons are partially inhibited at rest due to a constitutive CB1R activity removed by AM-251 and GDP-␤-S. Activation of CB1R via PTX-sensitive G proteins and cAMP/PKA pathway selectively depresses LTCCs that critically control the synchronized spontaneous firing and pulsatile release of gonadotropin-releasing hormone in GT1-7 neurons.

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Section: Introductionmentioning

confidence: 99%

L-type channel inhibition by CB1 cannabinoid receptors is mediated by PTX-sensitive G proteins and cAMP/PKA in GT1-7 hypothalamic neurons

et al. 2009

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“…Cannabis sativa preparations, the main psychoactive ingredient of which is Δ9-THC, produce intoxication characterized by sedation, cognitive dysfunction, failure to consolidate short-term memory, alteration in time assessment, perceptual changes, motor incoordination and poor executive function (Abood and Martin 1992;Dewey 1986;Hollister 1986;Pertwee 1988). In addition to exogenous cannabinoids, endocannabinoids including andamide and noladin ether, have also been identified.…”

Section: Introductionmentioning

confidence: 99%

Association study of the CNR1 gene exon 3 alternative promoter region polymorphisms and substance dependence

Herman

Kranzler

Cubells

et al. 2006

American J of Med Genetics Pt B

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An alternative promoter producing a novel 5′-untranslated region of cannabinoid receptor mRNA has recently been described in CNR1, the gene encoding the cannabinoid receptor protein. Single nucleotide polymorphisms (SNPs) adjacent to this site were reported to be associated with polysubstance abuse (Zhang et al. 2004). We examined the association of 4 SNPs (rs6928499, rs806379, rs1535255, rs2023239) in the distal region of intron 2 of CNR1 both with individual substance dependence diagnoses (i.e., alcohol, cocaine, and opioids), as well as with polysubstance dependence. The study samples consisted of European American and African American subjects with drug and or alcohol dependence (n=895), and controls (n = 472). Subjects were grouped as polysubstance dependent, opioid dependent, cocaine dependent, cannabis dependent and alcohol dependent. There was a modest association of marker rs1535255 with alcohol dependence, respectively (P=0.04), though with correction for multiple phenotype comparisons, this effect was not considered statistically significant. These findings fail to replicate the original report of an association between SNPs adjacent to an alternative CNR1 exon 3 transcription start site and polysubstance abuse.

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“…However, other studies have suggested that cannabinoids have opposite e ects under certain conditions. Thus, cannabinoids have been shown to increase basal cyclic AMP accumulation in various systems (for review see Pertwee, 1988). However, up to date, there is no evidence of a dual action of cannabinoids on cyclic AMP levels in the same system.…”

mentioning

confidence: 99%

Paradoxical action of the cannabinoid WIN 55,212‐2 in stimulated and basal cyclic AMP accumulation in rat globus pallidus slices

Maneuf

Brotchie

1997

British J Pharmacology

104

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The e ects of the synthetic cannabinoid WIN 55,212-2 on forskolin-stimulated and basal adenosine 3' : 5'-cyclic monophosphate (cyclic AMP) accumulation in globus pallidus slices were investigated. WIN 55,212-2 caused a concentration-dependent decrease in forskolin-stimulated cyclic AMP accumulation in globus pallidus slices (maximum inhibition 36% for 30 mM). This e ect was blocked by the cannabinoid receptor antagonist SR 141716A (100 mM). WIN 55,212-2 alone caused a concentration-dependent increase in cyclic AMP levels in unstimulated slices (maximum increase 52.6% for 100 mM). This e ect was also blocked by SR 141716A (100 mM). In either forskolin-stimulated or unstimulated conditions SR 1417161A (100 mM) did not a ect cyclic AMP levels.

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The central neuropharmcology of psychotropic cannabinoids

Cited by 160 publications

References 193 publications

L-type channel inhibition by CB1 cannabinoid receptors is mediated by PTX-sensitive G proteins and cAMP/PKA in GT1-7 hypothalamic neurons

L-type channel inhibition by CB1 cannabinoid receptors is mediated by PTX-sensitive G proteins and cAMP/PKA in GT1-7 hypothalamic neurons

Association study of the CNR1 gene exon 3 alternative promoter region polymorphisms and substance dependence

Paradoxical action of the cannabinoid WIN 55,212‐2 in stimulated and basal cyclic AMP accumulation in rat globus pallidus slices

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