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A Protocol for Measuring Cue Reactivity in a Rat Model of Cocaine Use Disorder
Published on: June 18, 2018
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Hippocampal Cannabinoid 1 Receptors Are Modulated Following Cocaine Self-administration in Male Rats
David De Sa Nogueira1,2, Romain Bourdy1, Rafael Alcala-Vida1
1Laboratoire de Neurosciences Cognitives Et Adaptatives (LNCA), Centre de La Recherche Nationale Scientifique, Université de Strasbourg, 12 rue Goethe, 67000, Strasbourg, France.
Molecular Neurobiology
|January 15, 2022
Summary
Cocaine use alters gene expression and epigenetic marks in brain reward circuits, particularly the hippocampus. These changes in endocannabinoid signaling contribute to long-term neuroplasticity and addiction-related behaviors.
Area of Science:
- Neuroscience
- Molecular Biology
- Addiction Research
Background:
- Cocaine addiction causes neuroplastic changes and behavioral issues.
- The endogenous cannabinoid system influences drug reward and cocaine-induced neural adaptations.
- Mechanisms of cocaine-induced transcriptional reprogramming in reward circuitry are not fully understood.
Purpose of the Study:
- To investigate long-term adaptations, including transcriptional and epigenetic modifications, induced by cocaine self-administration.
- To examine endocannabinoid gene expression and levels in rat brain regions after cocaine exposure.
- To explore the role of epigenetic processes in cocaine-induced neuronal plasticity.
Main Methods:
- Self-administration of cocaine (0.33 mg/kg IV, FR1, 10 days) in rats.
- Measurement of endocannabinoid gene expression (Cnr1) in reward-related brain regions.
- Mass spectrometry to quantify endocannabinoid levels in the hippocampus.
- Chromatin immunoprecipitation followed by qPCR to identify histone marks (H3K4Me3, H3K27Ac).
- Chromosome conformation capture to assess chromatin organization.
Main Results:
- Cocaine self-administration increased Cnr1 gene expression in multiple brain regions, most notably the hippocampus.
- Endocannabinoid levels were altered in the hippocampus.
- Activating histone marks (H3K4Me3, H3K27Ac) were enriched at endocannabinoid genes in the hippocampus.
- Cocaine intake induced spatial chromatin re-organization in the hippocampus and nucleus accumbens.
Conclusions:
- The hippocampus plays a crucial role in cocaine-induced neuroplasticity.
- Epigenetic modifications, including chromatin re-organization, are involved in neuronal responses to cocaine.
- Endocannabinoid signaling alterations and epigenetic changes contribute to the maladaptive behaviors associated with chronic cocaine use.
