Drug-induced Alterations in the Extracellular Signal-regulated Kinase (ERK) Signalling Pathway: Implications for Reinforcement and Reinstatement

Abstract

Drug addiction, characterized by high rates of relapse, is recognized as a kind of neuroadaptive disorder. Since the extracellular signal-regulated kinase (ERK) pathway is critical to neuroplasticity in the adult brain, understanding the role this pathway plays is important for understanding the molecular mechanism underlying drug addiction and relapse. Here, we review previous literatures that focus on the effects of exposure to cocaine, amphetamine, Delta(9)-tetrahydrocannabinol (THC), nicotine, morphine, and alcohol on ERK signaling in the mesocorticolimbic dopamine system; these alterations of ERK signaling have been thought to contribute to the drug's rewarding effects and to the long-term maladaptation induced by drug abuse. We then discuss the possible upstreams of the ERK signaling pathway activated by exposure of drugs of abuse and the environmental cues previously paired with drugs. Finally, we argue that since ERK activation is a key molecular process in reinstatement of conditioned place preference and drug self-administration, the pharmacological manipulation of the ERK pathway is a potential treatment strategy for drug addiction.

Ethanol‐Induced Extracellular Signal Regulated Kinase: Role of Dopamine D1 Receptors

“…The increased phosphorylation of ERK in the Acb, BSTL, and CeA was indeed suggested by Valjent and colleagues (2004) as an index to discriminate between psychoactive drugs with and psychoactive drugs without addictive properties; hence, these results confirm the prediction that, besides increasing DA transmission in the Acb, BSTL, and CeA (Carboni et al, 2000;Di Chiara, 2002;Di Chiara and Imperato, 1988;Yoshimoto et al, 2000), ethanol would also increase pERK signaling in the Acb and extended amygdala (Valjent et al, 2004). However, these results are at least partially at variance with previous data reporting inhibition or no effect of ethanol on ERK phosphorylation in vitro and in vivo (Chandler and Sutton, 2005;Kalluri and Ticku, 2002;Sanna et al, 2002;Smith and Navratilova, 2003; see also Zhai et al, 2008, for a comprehensive review). A possible explanation to interpret these apparent discrepancies might be due to the different experimental conditions (mice vs. rats, in vitro vs. in vivo experiments), doses and routes of administration, brain regions assayed (cerebral cortex and hippocampus vs. Acb and extended amygdala) and, finally, different time points at which ERK phosphorylation Sections considered were approximately between AP )1.8 mm and AP )2.3 mm from bregma, according to Paxinos and Watson (1998) rat brain atlas.…”

Extracellular Signal-Regulated Kinase in the Basolateral Amygdala, but not the Nucleus Accumbens Core, is Critical for Context-Response-Cocaine Memory Reconsolidation in Rats

“…On the day after the last extinction training session, rats were re-exposed to the cocaine-paired context for 15 min to initiate the destabilization and reconsolidation of cocaine memories (ie, cocaine-memory reactivation ;Fuchs et al, 2009; see Figure 1a). The levers were extended but cocaine was not infused upon lever pressing given that cocaine itself stimulates ERK phosphorylation (Zhai et al, 2008). Immediately after the session, rats received bilateral intra-BLA microinfusions of 5% DMSO/6% TWEEN vehicle (VEH) or U0126 (1.0 mg/0.5 ml/hemisphere, based on Miller and Marshall, 2005).…”

Alteraciones neurobiológicas en el alcoholismo: revisión

“…Besides, several studies have implicated the protein kinase C family of serine-threonine kinases in mediating both acute and chronic responses to ethanol exposure (Newton & Ron, 2007). Finally, the signalling pathway of MAP kinases, and specifically the extracellular-signal-regulated kinase (ERK) subfamily are modulated by ethanol, since ERK phosphorylation is reduced after acute and chronic exposure in rats and mice (Zhai, Li, Wang & Lu, 2008) and also in postmortem brain of alcoholic subjects (Erdozain et al, 2014).…”