Delta-9-tetrahydrocannabinol (Δ9-THC), the psychoactive principle of marijuana, has been shown to upregulate the mRNA levels of immediate-early genes in the rat brain. Using electrophoretic mobility-shift assay and onedimensional Western blot, we here report that Δ9-THC increases Activator protein-1 (AP-1) DNA-binding and Fos-related antigen activity in discrete areas of the rat brain. One hour after the intraperitoneal administration of Δ9-THC at a dose of 10 or 15 mg/kg, AP-1 DNA-binding activity in the nucleus accumbens increased by 33 and 49%, respectively, while Western blot showed an increase in both c-Fos, FosB, Fra-1 (Fos-related antigen) and Fra-2. In the cingulate cortex and caudate-putamen, Δ9-THC significantly increased AP-1 DNA-binding activity only at the highest dose used (57 and 71 %, respectively). While in the caudate-putamen the increase in AP-1 DNA binding was mainly due to an elevation of the c-Fos and FosB proteins, the same phenomenon depended on the FosB, Fra-1 and Fra-2 peptides in the cingulate cortex. The effect of Δ9-THC on the AP-1 DNA binding and the Fos-related antigens in the nucleus accumbens was blocked by the specific cannabinoid antagonist SR141716 A (3 mg/kg i.p.). Δ9-THC failed to modify Specificity protein 1 (Sp1) DNA-binding activity. The results indicate that Δ9-THC activates gene coding for AP-1 DNA-binding proteins by acting on cannabinoid receptors, and induces a different transcriptional program on the early-immediate gene of the Fos family, in different areas in the rat brain, suggesting that this mechanism might be involved in the central actions of cannabinoids. © European Neuroscience Association.

Δ9-Tetrahydrpcannabinol increases sequence-specific AP-1 DNA-binding activity and Fos-related antigens in the rat brain / A, Porcella; G, L Gessa; Pani, L.. - In: EUROPEAN JOURNAL OF NEUROSCIENCE. - ISSN 0953-816X. - 10:5(1998), pp. 1743-1751. [10.1046/j.1460-9568.1998.00175.x]

Δ9-Tetrahydrpcannabinol increases sequence-specific AP-1 DNA-binding activity and Fos-related antigens in the rat brain

Pani L.
1998

Abstract

Delta-9-tetrahydrocannabinol (Δ9-THC), the psychoactive principle of marijuana, has been shown to upregulate the mRNA levels of immediate-early genes in the rat brain. Using electrophoretic mobility-shift assay and onedimensional Western blot, we here report that Δ9-THC increases Activator protein-1 (AP-1) DNA-binding and Fos-related antigen activity in discrete areas of the rat brain. One hour after the intraperitoneal administration of Δ9-THC at a dose of 10 or 15 mg/kg, AP-1 DNA-binding activity in the nucleus accumbens increased by 33 and 49%, respectively, while Western blot showed an increase in both c-Fos, FosB, Fra-1 (Fos-related antigen) and Fra-2. In the cingulate cortex and caudate-putamen, Δ9-THC significantly increased AP-1 DNA-binding activity only at the highest dose used (57 and 71 %, respectively). While in the caudate-putamen the increase in AP-1 DNA binding was mainly due to an elevation of the c-Fos and FosB proteins, the same phenomenon depended on the FosB, Fra-1 and Fra-2 peptides in the cingulate cortex. The effect of Δ9-THC on the AP-1 DNA binding and the Fos-related antigens in the nucleus accumbens was blocked by the specific cannabinoid antagonist SR141716 A (3 mg/kg i.p.). Δ9-THC failed to modify Specificity protein 1 (Sp1) DNA-binding activity. The results indicate that Δ9-THC activates gene coding for AP-1 DNA-binding proteins by acting on cannabinoid receptors, and induces a different transcriptional program on the early-immediate gene of the Fos family, in different areas in the rat brain, suggesting that this mechanism might be involved in the central actions of cannabinoids. © European Neuroscience Association.
1998
10
5
1743
1751
Δ9-Tetrahydrpcannabinol increases sequence-specific AP-1 DNA-binding activity and Fos-related antigens in the rat brain / A, Porcella; G, L Gessa; Pani, L.. - In: EUROPEAN JOURNAL OF NEUROSCIENCE. - ISSN 0953-816X. - 10:5(1998), pp. 1743-1751. [10.1046/j.1460-9568.1998.00175.x]
A, Porcella; G, L Gessa; Pani, L.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1212126
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