title: Environmental enrichment counters cocaine abstinence-induced stress and brain reactivity to cocaine cues but fails to prevent the incubation effect.
abstract: 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.
authors.affiliation: Department of Psychology, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Thiel
authors.forename: Michael R
authors.initials: MR
authors.lastname: Painter
authors.forename: Nathan S
authors.initials: NS
authors.lastname: Pentkowski
authors.forename: Danut
authors.initials: D
authors.lastname: Mitroi
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Crawford
authors.forename: Janet L
authors.initials: JL
authors.lastname: Neisewander
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000523:psychology*; D003216:Conditioning, Operant / Q000187:drug effects; D003345:Corticosterone / Q000378:metabolism; D003463:Cues; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D004777:Environment; D005108:Extinction, Psychological / Q000187:drug effects; D066298:In Vitro Techniques; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D009042:Motivation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D012934:Social Isolation / Q000523:psychology*; D013315:Stress, Psychological / Q000517:prevention & control*; D013375:Substance Withdrawal Syndrome / Q000523:psychology; D019892:eIF-2 Kinase / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D003042:Cocaine; D003345:Corticosterone; D019892:eIF-2 Kinase