Journal
NEUROPHARMACOLOGY
Volume 180, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2020.108290
Keywords
Cocaine; Heroin; Natural rewards; Perineuronal nets; Prefrontal cortex
Categories
Funding
- Department of Psychobiology of UNED
- Spanish Ministry of Economy and Competitiveness [PSI2016-80541-P, 2016I073, 2017I042]
- Spanish Ministry of Health, Social Services and Equality (Network of Addictive Disorders of the Institute of Health Carlos III) [RTARD16/0017/0022]
- UNED (Plan for the Promotion of Research)
- European Union [JUST/2017/AGDRUG-806996-JUSTSO]
- BBVA Foundation
- Cajal Blue Brain Platform (CSIC/UPM, Spain)
- Ministry of Science and Innovation [BES-2011-043814]
- Plan for the Promotion of Research of UNED
- Ministry of Education of Spain
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Relapse into drug use is a significant problem for people recovering from addiction. The ability that conditioned cues have to reinstate and reinvigorate drug-seeking is potentiated over time (incubation of seeking), posing an additional difficulty for maintaining abstinence. While the prefrontal cortex has been involved in the incubation phenomenon and the extracellular matrix, perineuronal nets (PNNs) in particular, may play a vital role in brain plasticity associated to drug relapse, there are no comparative analyses between different drug classes and natural reinforcers. Here, we compare the effects of early (1 day) and protracted (30 days) withdrawal from to cocaine, heroin and sucrose self-administration on the total density and density per intensity range of PNNs of different territories of the prefrontal cortex of male Lewis rats. Our results show that cocaine self-administration increases the density of PNNs in the dorsal prelimbic, infralimbic and ventral orbitofrontal cortices, while protracted withdrawal reversesthis effect in the dorsal prelimbic cortex. Also, heroin self-administration in-creases the density of PNNs in the infralimbic cortex and ventral orbitofrontal cortices, but this effect is lost after 30 days of withdrawal in the infralimbic cortex. Finally, the self-administration of sucrose-sweetened water or the protracted withdrawal from this powerful reinforcer does not affect any of the PNN parameters analysed. Our results show that two different drugs of abuse (but not a natural reward) with specific pharmacological and physiological actions, differentially modulate PNNs in specific areas of the rodent prefrontal cortex with potential implications for the incubation of seeking phenomenon.
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