Fig. 6: Inhibition of the D1R downstream signalling in the medial prefrontal cortex prevents the memory capacity impairment mediated by the high dose of SKF 38393.
a Schematic of the experimental design. Mice were administered systemically with the impairing dose of SKF 38393 (0.1 mg/kg) or vehicle and injected locally in the medial prefrontal cortex (mPFC) with vehicle or the cAMP antagonist (RP)-cAMPS (Rpc, 0.025 µg/0.3 µl). The mice were then tested in the 6 different objects test (6-DOT) and subsequently assayed for PKA phosphorylation in both mPFC and striatum (STR) (red circles in the pictures). b Effects of the treatment with vehicle or SKF 38393 0.1 mg/kg or intra-mPFC of Rpc or the combination of both. Intra-mPFC Rpc alone did not change the performance in the 6-DOT, compared to vehicle. When given in combination with SKF, it prevented the impairing effects mediated by the high dose of SKF on WMC (One-way ANOVA: Treatment: F3,32 = 4.23; p = 0.0126, Tukey’s post hoc). c, d Representative immunoblots and quantification of PKA substrates phosphorylation. Intra-mPFC Rpc suppresses the PKA substrates phosphorylation increase caused by the impairing dose of SKF 38393in the mPFC (c) (One-way ANOVA: Treatment: F3,23 = 4.95; p = 0.0085, Tukey’s post hoc) and the hypoactivation of PKA in the STR of SKF (d) (One-way ANOVA: Treatment: F3,23 = 6.640; p = 0.0022, Tukey’s post hoc). Data in bar charts are presented as mean values  ±  SEM. *p < 0.05 vs vehicle. #p < 0.05 vs SKF 0.1 mg/kg. Source data are provided in the Source Data file.
