Effect of cocaine self-administration on striatal PKA-regulated signaling in male and female rats

Wendy J. Lynch, Drew D. Kiraly, Barbara J. Caldarone, Marina R. Picciotto, Jane R. Taylor

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


Rationale: Chronic cocaine produces changes in the dopamine (DA)/D1/cAMP/protein kinase A (PKA)-regulated signaling pathway that may underlie the development of addiction. Objective: Given sex differences in the progression to cocaine addiction, we examined the possibility that the PKA pathway is differentially activated by cocaine in male and female rats. Materials and methods: Rats were given 24-h access to cocaine (1.5 mg/kg) or saline for 7 days under a discrete trial procedure (four trials per hour). Rats were then retested on responding for cocaine under a progressive-ratio schedule after either 0 (no-delay retest) or 10 (10-day-delay retest) days of abstinence. Markers of PKA-regulated signaling in the striatum and nucleus accumbens were evaluated by Western blotting, including phosphorylation of DA and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) at Thr 34 and glutamate receptor 1 (GluR1) at Ser 845. Results: Compared to males, females had higher levels of DARPP-32 phosphorylated at the PKA site in the striatum. Increased phosphorylation of DARPP-32 at the PKA site was also seen in the nucleus accumbens of females compared to males, particularly among controls and rats tested after a 10-day abstinence period. DARPP-32 phosphorylation was also increased as a consequence of cocaine when tested after a 0-day abstinence period in male rats but not female rats. Conclusion: These findings indicate sex differences in PKA-regulated signaling in drug-naïve controls. Furthermore, these data suggest that regulation of PKA signaling by cocaine is differentially influenced in male and female rats as a consequence of cocaine exposure and cocaine abstinence period.

Original languageEnglish
Pages (from-to)263-271
Number of pages9
Issue number2
StatePublished - Apr 2007
Externally publishedYes


  • Cocaine
  • Dopamine and cAMP-regulated phosphoprotein of 32 kDa, DARPP-32
  • Glutamate receptor 1, GluR1
  • Protein kinase A, PKA
  • Self-administration
  • Sex differences


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