Place Preference Induced by Nucleus Accumbens Amphetamine Is Impaired by Antagonists of ERK or p38 MAP Kinases in Rats.

Abstract

The nucleus accumbens (NAc) plays a role in conditioned place preference (CPP). The authors tested the hypothesis that inhibition of mitogen-activated protein kinases (MAPKs) would inhibit NAc-amphetamine-produced CPP. Results confirmed that NAc amphetamine increased levels of the MAPK extracellular signal-regulated kinase (ERK). In CPP studies, NAc injections (0.5 microl per side) of the ERK inhibitor PD98059 (1.0-2.5 microg) or the p38 kinase inhibitor SB203580 (15-500 ng) dose dependently impaired CPP. The c-Jun-N-terminal kinase (JNK) inhibitor SP600125 (1.0-2.5 microg) failed to block the CPP effect. The drugs did not block amphetamine-induced motor activity. Results suggest that ERK and p38, but not JNK, MAPKs may be necessary for the establishment of NAc amphetamine-produced CPP and may also mediate other forms of reward-related learning dependent on NAc.

Extracellular Signal-Regulated Kinase in Nucleus Accumbens Mediates Propofol Self-Administration in Rats

“…The results showed that pretreatment with U0126 attenuated the propofol-maintained selfadministration, consistent with several other studies. For example, inhibition of ERK activity by intracerebroventricular pre-treatment with either PD98059 or U0126 decreases morphine-induced place preference [14]; ERK inhibition blocks THC-induced reward properties in the place-preference paradigm [15]; Amphetamine increases the levels of ERK, and NAc injections of the ERK inhibitor PD98059 dose-dependently impair amphetamine-induced place-preference [35]; and overexpressing ERK2 by virusmediated gene transfer increases the preference for environments previously paired with low doses of cocaine, whereas blocking ERK2 activity inhibits this cocaine-induced place conditioning [36]. Therefore, ERK signaling is critical for the downstream regulation of DA signal transmission in the NAc mediating the propofol self-administration and rewarding effects.…”

Knockout of ERK1 Enhances Cocaine-Evoked Immediate Early Gene Expression and Behavioral Plasticity

“…For example, pharmacological inhibition of MEK, the upstream activator of the two major ERK isoforms in the brain (ERK1 and ERK2), prevents both hippocampus-and amygdala-dependent memory formation (Atkins et al, 1998;Schafe et al, 1999;Adams and Sweatt, 2002). Pharmacological blockade of the Raf-MEK-ERK cascade also attenuates the development of a conditioned place preference to cocaine, amphetamine or MDMA (Valjent et al, 2000;Salzmann et al, 2003;Gerdjikov et al, 2004) and appears to modulate the development of psychomotor sensitization to cocaine (Pierce et al, 1999;Valjent et al, 2005). In addition, administration of psychomotor stimulant drugs increases ERK activity in several mesocorticolimbic brain regions associated with drug addiction (Valjent et al, 2000(Valjent et al, , 2005Adams et al, 2001; and the induction of immediate early genes (IEGs) in these brain regions is largely attenuated by pharmacological blockade of this pathway (Valjent et al, 2000;Salzmann et al, 2003;Ferguson and Robinson, 2004).…”

Blockage of glucocorticoid receptors during memory acquisition, retrieval and reconsolidation prevents the expression of morphine-induced conditioned place preferences in mice

“…To determine whether trained mice exhibited a significant conditioned place preference or aversion, preference scores were contrasted using repeated measures ANOVA with the day-factor as the within-groups variable and group-factor as the between-groups variable. This analysis was followed by between-group comparisons, which were completed with a post hoc analysis (LSD) test in SPSS 13.0 (Gerdjikov & Beninger, 2006). All behavioral data were collected from videorecordings was obtained by an investigator blind to the experimental conditions that performed offline manual scoring.…”