title: Sex differences in the effects of estradiol in the nucleus accumbens and striatum on the response to cocaine: neurochemistry and behavior.
abstract: BACKGROUND
  Females exhibit more rapid escalation of cocaine use and enhanced cocaine-taking behavior as compared to males. While ovarian hormones likely play a role in this increased vulnerability, research has yet to examine the role of estradiol in affecting the behavioral and neurological response to cocaine in a brain region- and sex-specific way.
  
  
  METHODS
  First, we examined stereotypy and locomotor sensitization after repeated cocaine administration (10 mg/kg i.p.) in intact (SHAM) and castrated (CAST) males, and ovariectomized (OVX) females treated with 5 μg estradiol benzoate (EB) or vehicle (OIL). Next, we used in vivo microdialysis to examine the effects of acute EB treatment on cocaine-induced DA in the regions mediating the display of these behaviors (i.e., the dorsolateral striatum, DLS; and the nucleus accumbens, NAc; respectively).
  
  
  RESULTS
  We find that EB enhances sensitization of cocaine-induced stereotypy in OVX females after 12 days of cocaine treatment, and after a 10-day withdrawal. Similarly, the OVX/EB females show enhanced locomotor sensitization compared to the other three groups on the same days. Using in vivo microdialysis to assess the neurochemical response, we find that EB rapidly enhances cocaine-induced DA in DLS dialysate of OVX females but not CAST males, and has no effect in NAc of either sex.
  
  
  CONCLUSIONS
  With these experiments, we show that there are sex differences in the effects of estradiol to preferentially enhance the response to cocaine in the DLS over the NAc in females, which may contribute to the preferential sensitization of stereotypy in females.
authors: Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, United States.
authors: Jennifer A
authors: JA
authors: Cummings
authors: Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, United States.
authors: Lakshmikripa
authors: L
authors: Jagannathan
authors: Department of Psychology, Schoolcraft College, Livonia, MI 48152, United States.
authors: Lisa R
authors: LR
authors: Jackson
authors: Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, United States; Department of Psychology, University of Michigan, Ann Arbor, MI 48109, United States; Department of Psychiatry, University of Michigan, Ann Arbor, MI 48109, United States. Electronic address: jbbecker@umich.edu.
authors: Jill B
authors: JB
authors: Becker
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000378:metabolism / Q000523:psychology; D003342:Corpus Striatum / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000008:administration & dosage*; D005260:Female; D008297:Male; D017551:Microdialysis / Q000379:methods; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009714:Nucleus Accumbens / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics
chemical_list: D004958:Estradiol; D003042:Cocaine
keywords: Behavioral sensitization; Dopamine; Drug abuse; Microdialysis; Sex differences