Acute and chronic modulation of striatal endocannabinoid‐mediated plasticity by nicotine. (2nd January 2018)

• Record Type: Journal Article
• Authors: Adermark, Louise; Morud, Julia; Lotfi, Amir; Ericson, Mia; Söderpalm, Bo
• Is Part Of: Addiction biology. Volume 24:Number 3(2019)
• Page Start: 355
• Page End: 363
• Publication Date: 2018-01-02
• Subjects: dopamine -- endocannabinoid -- synaptic plasticity; Substance abuse -- Periodicals; Substance abuse -- Physiological aspects -- Periodicals; Substance-Related Disorders -- periodicals; 616.86
• DOI: 10.1111/adb.12598
• Languages: English
• ISSNs: 1355-6215

Abstract

Abstract: The endocannabinoid (eCB) system modulates several phenomena related to addictive behaviors, and drug‐induced changes in eCB signaling have been postulated to be important mediators of physiological and pathological reward‐related synaptic plasticity. Here, we studied eCB‐mediated long‐term depression (eCB‐LTD) in the dorsolateral striatum, a brain region critical for acquisition of habitual and automatic behavior. We report that nicotine differentially affects ex vivo eCB signaling depending on previous exposure in vivo . In the nicotine‐naïve brain, nicotine facilitates eCB‐signaling and LTD, whereas tolerance develops to this facilitating effect after subchronic exposure in vivo . In the end, a progressive impairment of eCB‐induced LTD is established after protracted withdrawal from nicotine. Endocannabinoid‐LTD is reinstated 6 months after the last drug injection, but a brief period of nicotine re‐exposure is sufficient to yet again impair eCB‐signaling. LTD induced by the cannabinoid 1 receptor agonist WIN55, 212‐2 is not affected, suggesting that nicotine modulates eCB production or release. Nicotine‐induced facilitation of eCB‐LTD is occluded by the dopamine D2 receptor agonist quinpirole, and by the muscarinic acetylcholine receptor antagonist scopolamine. In addition, the same compounds restore eCB‐LTD during protracted withdrawal. Nicotine may thus modulate eCB‐signaling by affecting dopaminergic and cholinergic neurotransmission in a long‐lasting manner. Overall, the data presented here suggest that nicotine facilitates eCB‐LTD in the initial phase, which putatively could promote neurophysiological and behavioral adaptations to the drug. Protracted withdrawal, however, impairs eCB‐LTD, which may influence or affect the ability to maintain cessation. Abstract : Acute nicotine exposure facilitates striatal eCB signaling, which might promote habit formation and addiction. In contrast, repeated administration to nicotine in vivo, followed by protracted abstinence, results in impaired eCB signaling for several months, which might affect behavioral flexibility and putatively the recovery from addiction. Dopamine D2 receptors play a key role in mediating both these effects.