TY - JOUR
T1 - Environmental living conditions introduced during forced abstinence alter cocaine-seeking behavior and Fos protein expression
AU - Thiel, K. J.
AU - Pentkowski, N. S.
AU - Peartree, N. A.
AU - Painter, M. R.
AU - Neisewander, Janet
N1 - Funding Information:
This work was supported by grants R01DA11064 , R21DA023123 , and F31DA023746 from the National Institute on Drug Abuse (NIDA). The content is solely the responsibility of the authors and does not necessarily represent the official view of NIDA or the National Institutes of Health. The authors wish to thank Lara Pockros, Lindsey Robertson, and Ben Engelhardt for their expert technical assistance throughout various phases of the study.
PY - 2010/12/29
Y1 - 2010/12/29
N2 - Environmental enrichment (EE) introduced during abstinence from cocaine self-administration is protective in reducing cue-elicited incentive motivation for cocaine in rats. This study examined neural activation associated with this protective effect of EE using Fos protein expression as a marker. Rats were trained to press a lever reinforced by cocaine (0.75 mg/kg/0.1 mL infusion) and light and tone cues across 15 consecutive days during which they were all housed in isolated conditions (IC). Rats were then assigned to either remain in IC, or to live in pair-housed conditions (PC) or EE for 30 days of forced abstinence from cocaine. Subsequently, cocaine-seeking behavior (lever presses without cocaine reinforcement) elicited by response-contingent cue presentations was assessed for 90 min, after which the rats' brains were immediately harvested for Fos protein immunohistochemistry. EE attenuated, whereas IC enhanced, cue-elicited cocaine-seeking behavior relative to PC. Also, within the prelimbic and orbitofrontal cortices and basolateral amygdala, IC enhanced, whereas EE reduced, Fos expression relative to PC. Furthermore, EE attenuated Fos expression in the infralimbic and anterior cingulate cortices, the nucleus accumbens (core and shell), bed nucleus of the stria terminalis, and ventral tegmental area, evident as a reduction relative to both PC and IC. In contrast, IC enhanced Fos expression in the dorsal caudate putamen, substantia nigra, and central amygdala, evident as an increase relative to both PC and EE. These results suggest that EE blunts neural activation throughout the mesocorticolimbic circuitry involved in cue-elicited incentive motivation for cocaine, whereas IC enhances activation primarily within the nigrostriatal dopamine pathway. These findings have important implications for understanding and treating drug-conditioned craving in humans.
AB - Environmental enrichment (EE) introduced during abstinence from cocaine self-administration is protective in reducing cue-elicited incentive motivation for cocaine in rats. This study examined neural activation associated with this protective effect of EE using Fos protein expression as a marker. Rats were trained to press a lever reinforced by cocaine (0.75 mg/kg/0.1 mL infusion) and light and tone cues across 15 consecutive days during which they were all housed in isolated conditions (IC). Rats were then assigned to either remain in IC, or to live in pair-housed conditions (PC) or EE for 30 days of forced abstinence from cocaine. Subsequently, cocaine-seeking behavior (lever presses without cocaine reinforcement) elicited by response-contingent cue presentations was assessed for 90 min, after which the rats' brains were immediately harvested for Fos protein immunohistochemistry. EE attenuated, whereas IC enhanced, cue-elicited cocaine-seeking behavior relative to PC. Also, within the prelimbic and orbitofrontal cortices and basolateral amygdala, IC enhanced, whereas EE reduced, Fos expression relative to PC. Furthermore, EE attenuated Fos expression in the infralimbic and anterior cingulate cortices, the nucleus accumbens (core and shell), bed nucleus of the stria terminalis, and ventral tegmental area, evident as a reduction relative to both PC and IC. In contrast, IC enhanced Fos expression in the dorsal caudate putamen, substantia nigra, and central amygdala, evident as an increase relative to both PC and EE. These results suggest that EE blunts neural activation throughout the mesocorticolimbic circuitry involved in cue-elicited incentive motivation for cocaine, whereas IC enhances activation primarily within the nigrostriatal dopamine pathway. These findings have important implications for understanding and treating drug-conditioned craving in humans.
KW - Cocaine cues
KW - Craving
KW - Environmental enrichment
KW - Immediate early gene
KW - Incentive motivation
KW - Neurocircuitry
UR - http://www.scopus.com/inward/record.url?scp=78650172959&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78650172959&partnerID=8YFLogxK
U2 - 10.1016/j.neuroscience.2010.10.001
DO - 10.1016/j.neuroscience.2010.10.001
M3 - Article
C2 - 20933585
AN - SCOPUS:78650172959
SN - 0306-4522
VL - 171
SP - 1187
EP - 1196
JO - Neuroscience
JF - Neuroscience
IS - 4
ER -