Cannabidiol treatment prevents drug reinstatement and the molecular alterations evoked by amphetamine on receptors and enzymes from dopaminergic and endocannabinoid systems in rats
Copyright © 2022. Published by Elsevier Inc..
In psychostimulant drug addiction, relapse is the most concerning outcome to be managed, considering there is no approved treatment for this neuropsychiatric condition. Here, we investigated the effects of the CBD treatment on the relapse behavior triggered by stress, after being submitted to the amphetamine (AMPH)-induced conditioned place preference (CPP) in rats. To elucidate the mechanisms of action underlying the CBD treatment, we evaluated the neuroadaptations on dopaminergic and endocannabinoid targets in the ventral striatum (VS) and ventral tegmental area (VTA) of the brain. Animals received d,l-AMPH (4 mg/kg, i.p.) or vehicle in the CPP paradigm for 8 days. Following the first CPP test, animals were treated with CBD (10 mg/kg, i.p.) or its vehicle for 5 days and subsequently submitted to forced swim stress protocol to induce AMPH-CPP relapse. Behavioral findings showed that CBD treatment prevented AMPH-reinstatement, also exerting anxiolytic activity. At the molecular level, in the VTA, CBD restored the CB1R levels decreased by AMPH-exposure, increased NAPE-PLD, and decreased FAAH levels. In the VS, the increase of D1R and D2R, as well as the decrease of DAT levels induced by AMPH were restored by CBD treatment. The current outcomes evidence a substantial preventive action of the CBD on the AMPH-reinstatement evoked by stress, also involving neuroadaptations in both dopaminergic and endocannabinoid systems in brain areas closely involved in the addiction. Although further studies are needed, these findings support the therapeutic potential of CBD in AMPH-relapse prevention.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:218 |
|---|---|
| Enthalten in: |
Pharmacology, biochemistry, and behavior - 218(2022) vom: 01. Juli, Seite 173427 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Metz, Vinícia Garzella [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 09.08.2022 Date Revised 23.08.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.pbb.2022.173427 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM343314029 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM343314029 | ||
| 003 | DE-627 | ||
| 005 | 20231226020146.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.pbb.2022.173427 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1144.xml |
| 035 | |a (DE-627)NLM343314029 | ||
| 035 | |a (NLM)35810923 | ||
| 035 | |a (PII)S0091-3057(22)00106-X | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Metz, Vinícia Garzella |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Cannabidiol treatment prevents drug reinstatement and the molecular alterations evoked by amphetamine on receptors and enzymes from dopaminergic and endocannabinoid systems in rats |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 09.08.2022 | ||
| 500 | |a Date Revised 23.08.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022. Published by Elsevier Inc. | ||
| 520 | |a In psychostimulant drug addiction, relapse is the most concerning outcome to be managed, considering there is no approved treatment for this neuropsychiatric condition. Here, we investigated the effects of the CBD treatment on the relapse behavior triggered by stress, after being submitted to the amphetamine (AMPH)-induced conditioned place preference (CPP) in rats. To elucidate the mechanisms of action underlying the CBD treatment, we evaluated the neuroadaptations on dopaminergic and endocannabinoid targets in the ventral striatum (VS) and ventral tegmental area (VTA) of the brain. Animals received d,l-AMPH (4 mg/kg, i.p.) or vehicle in the CPP paradigm for 8 days. Following the first CPP test, animals were treated with CBD (10 mg/kg, i.p.) or its vehicle for 5 days and subsequently submitted to forced swim stress protocol to induce AMPH-CPP relapse. Behavioral findings showed that CBD treatment prevented AMPH-reinstatement, also exerting anxiolytic activity. At the molecular level, in the VTA, CBD restored the CB1R levels decreased by AMPH-exposure, increased NAPE-PLD, and decreased FAAH levels. In the VS, the increase of D1R and D2R, as well as the decrease of DAT levels induced by AMPH were restored by CBD treatment. The current outcomes evidence a substantial preventive action of the CBD on the AMPH-reinstatement evoked by stress, also involving neuroadaptations in both dopaminergic and endocannabinoid systems in brain areas closely involved in the addiction. Although further studies are needed, these findings support the therapeutic potential of CBD in AMPH-relapse prevention | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Addiction | |
| 650 | 4 | |a Conditioned place preference | |
| 650 | 4 | |a Psychostimulants | |
| 650 | 4 | |a Ventral striatum | |
| 650 | 4 | |a Ventral tegmental area | |
| 650 | 7 | |a Endocannabinoids |2 NLM | |
| 650 | 7 | |a Cannabidiol |2 NLM | |
| 650 | 7 | |a 19GBJ60SN5 |2 NLM | |
| 650 | 7 | |a Amphetamine |2 NLM | |
| 650 | 7 | |a CK833KGX7E |2 NLM | |
| 650 | 7 | |a Dopamine |2 NLM | |
| 650 | 7 | |a VTD58H1Z2X |2 NLM | |
| 700 | 1 | |a da Rosa, Jéssica Leandra Oliveira |e verfasserin |4 aut | |
| 700 | 1 | |a Rossato, Domenika Rubert |e verfasserin |4 aut | |
| 700 | 1 | |a Burger, Marilise Escobar |e verfasserin |4 aut | |
| 700 | 1 | |a Pase, Camila Simonetti |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Pharmacology, biochemistry, and behavior |d 1973 |g 218(2022) vom: 01. Juli, Seite 173427 |w (DE-627)NLM000022721 |x 1873-5177 |7 nnns |
| 773 | 1 | 8 | |g volume:218 |g year:2022 |g day:01 |g month:07 |g pages:173427 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.pbb.2022.173427 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 218 |j 2022 |b 01 |c 07 |h 173427 | ||