Abstract
Although extracellular signal-regulated kinase (ERK) activity is essential for the acquisition of a variety of associative learning tasks, its involvement in the acquisition and extinction of ethanol (EtOH)-induced conditioned place preference (CPP) remains unknown. Therefore, in these experiments we examined the effects of the ERK-kinase (MEK)-inhibitor SL327 on acquisition and expression of EtOH-CPP as well as the dose- and time-dependent effects of SL327 on CPP extinction. The parametric findings of Experiment 1 showed that three 30-min (but not 15- or 5-min) non-reinforced trials were required to completely extinguish EtOH-CPP in male, DBA/2J mice. In Experiments 2 and 3, SL327 (30 and 50. mg/kg), administered 30 or 90. min prior to extinction trials, was unable to impair EtOH-CPP extinction. Experiment 4 showed that SL327 (50. mg/kg) had no effect on acquisition of EtOH-CPP or the development of EtOH-induced sensitization during conditioning. When administered prior to testing in Experiments 5 and 6, SL327 did not alter expression of EtOH-CPP but did reduce test activity. Importantly, SL327 significantly reduced pERK protein levels when assessed in the dorsal striatum and motor cortex (Experiment 7). Together, these data suggest that EtOH-related learning and EtOH reward in mice, as assessed with CPP, are not impaired by the systemically administered MEK-inhibitor SL327.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 399-407 |
| Number of pages | 9 |
| Journal | Behavioural Brain Research |
| Volume | 217 |
| Issue number | 2 |
| DOIs | |
| State | Published - Mar 1 2011 |
Fingerprint
Keywords
- Conditioned place preference
- DBA/2J
- ERK
- Ethanol
- Extinction
- SL327
ASJC Scopus subject areas
- Behavioral Neuroscience
Cite this
Inhibition of extracellular signal-regulated kinase (ERK) activity with SL327 does not prevent acquisition, expression, and extinction of ethanol-seeking behavior in mice. / Groblewski, Peter A.; Franken, Frederick H.; Cunningham, Christopher.
In: Behavioural Brain Research, Vol. 217, No. 2, 01.03.2011, p. 399-407.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibition of extracellular signal-regulated kinase (ERK) activity with SL327 does not prevent acquisition, expression, and extinction of ethanol-seeking behavior in mice
AU - Groblewski, Peter A.
AU - Franken, Frederick H.
AU - Cunningham, Christopher
PY - 2011/3/1
Y1 - 2011/3/1
N2 - Although extracellular signal-regulated kinase (ERK) activity is essential for the acquisition of a variety of associative learning tasks, its involvement in the acquisition and extinction of ethanol (EtOH)-induced conditioned place preference (CPP) remains unknown. Therefore, in these experiments we examined the effects of the ERK-kinase (MEK)-inhibitor SL327 on acquisition and expression of EtOH-CPP as well as the dose- and time-dependent effects of SL327 on CPP extinction. The parametric findings of Experiment 1 showed that three 30-min (but not 15- or 5-min) non-reinforced trials were required to completely extinguish EtOH-CPP in male, DBA/2J mice. In Experiments 2 and 3, SL327 (30 and 50. mg/kg), administered 30 or 90. min prior to extinction trials, was unable to impair EtOH-CPP extinction. Experiment 4 showed that SL327 (50. mg/kg) had no effect on acquisition of EtOH-CPP or the development of EtOH-induced sensitization during conditioning. When administered prior to testing in Experiments 5 and 6, SL327 did not alter expression of EtOH-CPP but did reduce test activity. Importantly, SL327 significantly reduced pERK protein levels when assessed in the dorsal striatum and motor cortex (Experiment 7). Together, these data suggest that EtOH-related learning and EtOH reward in mice, as assessed with CPP, are not impaired by the systemically administered MEK-inhibitor SL327.
AB - Although extracellular signal-regulated kinase (ERK) activity is essential for the acquisition of a variety of associative learning tasks, its involvement in the acquisition and extinction of ethanol (EtOH)-induced conditioned place preference (CPP) remains unknown. Therefore, in these experiments we examined the effects of the ERK-kinase (MEK)-inhibitor SL327 on acquisition and expression of EtOH-CPP as well as the dose- and time-dependent effects of SL327 on CPP extinction. The parametric findings of Experiment 1 showed that three 30-min (but not 15- or 5-min) non-reinforced trials were required to completely extinguish EtOH-CPP in male, DBA/2J mice. In Experiments 2 and 3, SL327 (30 and 50. mg/kg), administered 30 or 90. min prior to extinction trials, was unable to impair EtOH-CPP extinction. Experiment 4 showed that SL327 (50. mg/kg) had no effect on acquisition of EtOH-CPP or the development of EtOH-induced sensitization during conditioning. When administered prior to testing in Experiments 5 and 6, SL327 did not alter expression of EtOH-CPP but did reduce test activity. Importantly, SL327 significantly reduced pERK protein levels when assessed in the dorsal striatum and motor cortex (Experiment 7). Together, these data suggest that EtOH-related learning and EtOH reward in mice, as assessed with CPP, are not impaired by the systemically administered MEK-inhibitor SL327.
KW - Conditioned place preference
KW - DBA/2J
KW - ERK
KW - Ethanol
KW - Extinction
KW - SL327
UR - http://www.scopus.com/inward/record.url?scp=78650418321&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78650418321&partnerID=8YFLogxK
U2 - 10.1016/j.bbr.2010.11.018
DO - 10.1016/j.bbr.2010.11.018
M3 - Article
C2 - 21074569
AN - SCOPUS:78650418321
VL - 217
SP - 399
EP - 407
JO - Behavioural Brain Research
JF - Behavioural Brain Research
SN - 0166-4328
IS - 2
ER -