Phytocannabinoids and endocannabinoids as modulators of cocaine reinforcement in mice
Cocaine use profoundly disrupts the neuronal circuits that regulate reward processing, motivation and decision making, resulting in long-lasting neuroplastic adaptations in the mesocorticolimbic system. The endocannabinoid system (ECS) shows promise in regulating addiction-related maladaptations due...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/688953 |
| Acceso en línea: | http://hdl.handle.net/10803/688953 |
| Access Level: | acceso abierto |
| Palabra clave: | Cocaine Addiction Cannabidiol Endocannabinoids Reinforcement Cocaïna Addicció Reforçament 616.8 |
| Sumario: | Cocaine use profoundly disrupts the neuronal circuits that regulate reward processing, motivation and decision making, resulting in long-lasting neuroplastic adaptations in the mesocorticolimbic system. The endocannabinoid system (ECS) shows promise in regulating addiction-related maladaptations due to its involvement in synaptic plasticity and neurotransmitter release and its widespread distribution throughout the mesocorticolimbic system. Here, we aimed to investigate the effects of different therapeutic interventions targeting the ECS on cocaine-induced behaviours and molecular alterations in adult male CB1 mice, including the use of phytocannabinoids, specifically cannabidiol (CBD) and cannabidiolic acid (CBDA), as well as the inhibition of fatty acid amide hydrolase (FAAH) using URB597. Our findings revealed that CBD inhibited cocaine self-administration, without preventing incubation of cocaine craving during abstinence. On the other hand, increasing the levels of endocannabinoids through the inhibition of FAAH modulated the early neuroplastic and behavioural impairments caused by cocaine and reduced several behaviours related to cocaine reinforcement These effects were accompanied by changes in neural activation in the nucleus accumbens. Lastly, CBDA exhibited anti-nociceptive and reduced despair-like behaviour but did not modulate cocaine reward. Altogether, our findings support the therapeutic potential of pharmacological strategies targeting the ECS in the treatment of cocaine addiction. |
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