Estradiol (17β-estradiol; E2758, Sigma-Aldrich, St. Louis, MO) was dissolved in cottonseed oil to a final concentration of 2 μg/0.1 ml and was injected s.c. at a volume of 0.1 ml. The mGluR5 antagonist MPEP (1212, Tocris, Minneapolis, MN) was dissolved in sterile saline (1 mg/ml/kg) and injected i.p. This dose of MPEP has been shown to block estradiol-induced changes in dendritic spines within the NAc (Peterson et al., 2014 (link)), as well as estradiol enhancement of behavioral sensitization (Sircar and Kim, 1999 (link); Martinez et al., 2014 (link)), in OVX female rats. The mGluR5-positive allosteric modulator 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB; 3235, Tocris) was dissolved in 10% Tween-80 (low CDPPB, 10 mg/ml/kg; high CDPPB, 25 mg/2 ml/kg) and injected i.p. The 10 mg/ml/kg dose of CDPPB mimics the effects of estradiol on dendritic spine density in the NAc in OVX females (Gross et al., 2016 (link)). Cocaine (cocaine hydrochloride; 0406-1520-53, Mallinckrodt, St. Louis, MO) was dissolved in sterile PBS (9.3 mg/ml) and infused i.v. (1.5 mg/kg/infusion). Previous work has shown that under extended access conditions, estradiol treatment enhances cocaine intake in OVX females self-administering at this dose (Ramôa et al., 2013 (link)).
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