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Basal and cocaine-induced sex differences in the DARPP-32-mediated signaling pathway.

Abstract：

RATIONALE:Behavioral and dopamine responses to cocaine are sexually dimorphic: Female rats exhibit higher levels of locomotor and reward-associated behaviors after cocaine administration and dopamine release than do males. Activation of the dopamine- and cAMP-regulated phosphoprotein of Mr 32 kDa (DARPP-32) intracellular cascade mediates responses to cocaine. OBJECTIVE:To examine the possibility that acute cocaine administration alters the DARPP-32 cascade in a sexually dimorphic pattern. MATERIALS AND METHODS:Male and female rats received either saline or cocaine (30 mg/kg). Protein levels of DARPP-32, phosphorylation of DARPP-32 at the Thr34 site (P-Thr34-DARPP-32), protein phosphatase 1 (PP-1), and protein phosphatase 2B (PP-2B) in nucleus accumbens were measured via Western blot analysis. RESULTS:Females had higher protein levels of DARPP-32, P-Thr34-DARPP-32, calcineurin A (CaN-A; catalytic subunit of PP-2B), and calcineurin B (CaN-B; regulatory subunit of PP-2B) than males 5 min after saline treatment. In females, CaN-A protein levels were also higher at 15 min and PP-1 protein levels were higher 30 min after saline administration than males. In male rats, cocaine significantly increased CaN-A protein levels at 30 min and CaN-B protein levels at 15 min. In females, cocaine administration significantly decreased protein levels of DARPP-32, P-Thr34-DARPP-32, and CaN-A at 45 min but increased PP-1 protein levels at 30 min. Overall, males had higher activation of the DARPP-32 pathway after cocaine administration than did females. CONCLUSION:These novel results show that basal and cocaine-induced sex differences in the DARPP-32/PP-1 cascade may be responsible for the sexual dimorphism in acute cocaine-induced behavioral responses.

journal_name

Psychopharmacology (Berl)

journal_title

Psychopharmacology

authors

Zhou L,Nazarian A,Sun WL,Jenab S,Quinones-Jenab V

doi

10.1007/s00213-008-1388-0

subject

Has Abstract

pub_date

2009-03-01 00:00:00

pages

175-83

issue

1

eissn

0033-3158

issn

1432-2072

journal_volume

203

pub_type

杂志文章

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