TY - JOUR
T1 - Environmental enrichment counters cocaine abstinence-induced stress and brain reactivity to cocaine cues but fails to prevent the incubation effect
AU - Thiel, Kenneth J.
AU - Painter, Michael R.
AU - Pentkowski, Nathan S.
AU - Mitroi, Danut
AU - Crawford, Cynthia A.
AU - Neisewander, Janet
PY - 2012/3
Y1 - 2012/3
N2 - Environmental enrichment (EE) during a period of forced abstinence attenuates incentive motivational effects of cocaine-paired stimuli. Here we examined whether EE during forced abstinence from cocaine self-administration would prevent time-dependent increases in cue-elicited cocaine-seeking behavior (i.e. the incubation effect). Rats were trained to self-administer cocaine, which was paired with light/tone cues, for 15 days while living in isolated conditions (IC). Controls received yoked saline infusions. Subsequently, rats were assigned to live in either continued IC or EE for either 1 or 21 days of forced abstinence prior to a test for cocaine-seeking behavior. During testing, responding resulted only in presentation of the light/tone cues. Contrary to our prediction, cocaine-seeking behavior increased over time regardless of living condition during abstinence; however, EE attenuated cocaine-seeking behavior relative to IC regardless of length of abstinence. Brains were harvested and trunk blood was collected immediately after the 60-minute test and later assayed. Results indicated that short-term EE elevated hippocampal brain-derived neurotrophic factor and reduced plasma corticosterone compared with IC. Furthermore, 21 days of EE during forced abstinence prevented increases in the cue-elicited amygdala phosphorylated extracellular signal-regulated kinase expression that was observed in IC rats. These findings suggest that EE attenuates incentive motivational effects of cocaine cues through a mechanism other than preventing the incubation effect, perhaps involving reduction of stress and neural activity in response to cocaine-paired cues during acute withdrawal.
AB - Environmental enrichment (EE) during a period of forced abstinence attenuates incentive motivational effects of cocaine-paired stimuli. Here we examined whether EE during forced abstinence from cocaine self-administration would prevent time-dependent increases in cue-elicited cocaine-seeking behavior (i.e. the incubation effect). Rats were trained to self-administer cocaine, which was paired with light/tone cues, for 15 days while living in isolated conditions (IC). Controls received yoked saline infusions. Subsequently, rats were assigned to live in either continued IC or EE for either 1 or 21 days of forced abstinence prior to a test for cocaine-seeking behavior. During testing, responding resulted only in presentation of the light/tone cues. Contrary to our prediction, cocaine-seeking behavior increased over time regardless of living condition during abstinence; however, EE attenuated cocaine-seeking behavior relative to IC regardless of length of abstinence. Brains were harvested and trunk blood was collected immediately after the 60-minute test and later assayed. Results indicated that short-term EE elevated hippocampal brain-derived neurotrophic factor and reduced plasma corticosterone compared with IC. Furthermore, 21 days of EE during forced abstinence prevented increases in the cue-elicited amygdala phosphorylated extracellular signal-regulated kinase expression that was observed in IC rats. These findings suggest that EE attenuates incentive motivational effects of cocaine cues through a mechanism other than preventing the incubation effect, perhaps involving reduction of stress and neural activity in response to cocaine-paired cues during acute withdrawal.
KW - Brain-derived neurotrophic factor (BDNF)
KW - corticosterone
KW - craving
KW - drug-seeking behavior
KW - extracellular signal-regulated kinase (ERK)
KW - incentive motivation
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UR - http://www.scopus.com/inward/citedby.url?scp=84857652792&partnerID=8YFLogxK
U2 - 10.1111/j.1369-1600.2011.00358.x
DO - 10.1111/j.1369-1600.2011.00358.x
M3 - Article
C2 - 21812872
AN - SCOPUS:84857652792
SN - 1355-6215
VL - 17
SP - 365
EP - 377
JO - Addiction Biology
JF - Addiction Biology
IS - 2
ER -