Stress augments the rewarding memory of cocaine via the activation of brainstem‐reward circuitry. (26th February 2018)

• Record Type: Journal Article
• Authors: Shinohara, Fumiya; Asaoka, Yuta; Kamii, Hironori; Minami, Masabumi; Kaneda, Katsuyuki
• Is Part Of: Addiction biology. Volume 24:Number 3(2019)
• Page Start: 509
• Page End: 521
• Publication Date: 2018-02-26
• Subjects: addiction -- dopamine -- laterodorsal tegmental nucleus -- medial prefrontal cortex -- noradrenaline -- ventral tegmental area; Substance abuse -- Periodicals; Substance abuse -- Physiological aspects -- Periodicals; Substance-Related Disorders -- periodicals; 616.86
• DOI: 10.1111/adb.12617
• Languages: English
• ISSNs: 1355-6215

Abstract

Abstract: Effects of stress on the reward system are well established in the literature. Although previous studies have revealed that stress can reinstate extinguished addictive behaviors related to cocaine, the effects of stress on the rewarding memory of cocaine are not fully understood. Here, we provide evidence that stress potentiates the expression of rewarding memory of cocaine via the activation of brainstem‐reward circuitry using a cocaine‐induced conditioned place preference (CPP) paradigm combined with restraint stress in rats. The rats exposed to 30‐minute restraint stress immediately before posttest exhibited significantly larger CPP scores compared with non‐stressed rats. Intra‐laterodorsal tegmental nucleus (LDT) microinjection of a β or α2 adrenoceptor antagonist attenuated the stress‐induced enhancement of cocaine CPP. Consistent with this observation, intra‐LDT microinjection of a β or α2 adrenoceptor agonist before posttest increased cocaine CPP. Additionally, intra‐ventral tegmental area (VTA) microinjection of antagonists for the muscarinic acetylcholine, nicotinic acetylcholine or glutamate receptors attenuated the stress‐induced enhancement of cocaine CPP. Finally, intra‐medial prefrontal cortex (mPFC) microinjection of a D1 receptor antagonist also reduced the stress‐induced enhancement of cocaine CPP. These findings suggest a mechanism wherein the LDT is activated by noradrenergic input from the locus coeruleus, leading to the activation of VTA dopamine neurons via both cholinergic and glutamatergic transmission and the subsequent excitation of the mPFC to enhance the memory of cocaine‐induced reward value. Abstract : By combining a cocaine‐induced conditioned place preference paradigm with restraint stress, to which rats were exposed immediately before posttest, we provide evidence that stress potentiates the expression of rewarding memory of cocaine via the activation of brainstem‐reward circuitry. Intracranial microinjections revealed that under the stress condition, the laterodorsal tegmental nucleus is activated by noradrenergic input from the locus coeruleus via β and α2 adrenoceptors, leading to the activation of ventral tegmental area dopamine neurons through both cholinergic and glutamatergic transmissions. Subsequently, the medial prefrontal cortex is excited by D1 receptor stimulation, resulting in the enhancement of the cocaine‐induced rewarding memory.