title: Sexually dimorphic intracellular responses after cocaine-induced conditioned place preference expression.
abstract: Sex differences in cocaine's mechanisms of action and behavioral effects have been widely reported. However, little is known about how sex influences intracellular signaling cascades involved with drug-environment associations. We investigated whether ERK/CREB intracellular responses in the mesocorticolimbic circuitry underlying cocaine environmental associations are sexually dimorphic. We used a standard 4 day conditioned place preference (CPP) paradigm using 20mg/kg cocaine-a dose that induced CPP in male and female Fischer rats. In the nucleus accumbens (NAc) following CPP expression, cocaine treated animals showed increased phosphorylated ERK (pERK), phosphorylated CREB (pCREB) and ΔFosB protein levels. In the hippocampus (HIP) and caudate putamen (CPu), pERK and FosB/ΔFosB levels were also increased, respectively. Cocaine females had a larger change in HIP pERK and CPu ΔFosB levels than cocaine males; partly due to lower protein levels in saline female rats when compared to saline males. Prefrontal cortex (PfC) pCREB levels increased in cocaine males, but not females, whereas PfC pERK levels were increased in cocaine females, but not males. CPP scores were positively correlated to NAc pERK, HIP pERK and CPu FosB protein levels, suggesting that similar to males, the ERK/CREB intracellular pathway in mesocorticolimbic regions undergoes cocaine induced neuroplasticity in female rats. However, there seem to be intrinsic (basal) sexual dimorphisms in this pathway that may contribute to responses expressed after cocaine-CPP. Taken together, our results suggest that cellular responses associated with the expression of learned drug-environment associations may play an important role in sex differences in cocaine addiction and relapse.
authors.affiliation: Department of Psychology, Hunter College, CUNY, 695 Park Avenue, New York, NY 10065, USA. stephanienygard@gmail.com
authors.forename: Stephanie K
authors.initials: SK
authors.lastname: Nygard
authors.forename: Anthony
authors.initials: A
authors.lastname: Klambatsen
authors.forename: Ruhal
authors.initials: R
authors.lastname: Hazim
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Eltareb
authors.forename: Jeff C
authors.initials: JC
authors.lastname: Blank
authors.forename: Anna J
authors.initials: AJ
authors.lastname: Chang
authors.forename: Vanya
authors.initials: V
authors.lastname: Quinones-Jenab
authors.forename: Shirzad
authors.initials: S
authors.lastname: Jenab
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000378:metabolism*; D003216:Conditioning, Operant / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D008297:Male; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012727:Sex Characteristics; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D018765:Dopamine Uptake Inhibitors; C483820:Fosb protein, rat; D016760:Proto-Oncogene Proteins c-fos; D048049:Extracellular Signal-Regulated MAP Kinases; D003042:Cocaine