Fig. 1: Regulation of Dcc expression in the VTA by AMPH in adolescence is sexually dimorphic.

a Dcc mRNA is expressed by 99% of dopamine neurons in the VTA of both male and female mice⁵⁹. b The microRNA miR-218 represses Dcc mRNA expression^58,102. c Timeline of experiments in early adolescence. Male and female mice were exposed to a recreational-like amphetamine (AMPH, 4 mg/kg) regimen from P21 ± 1 to P31 ± 1⁶³. One week later, Dcc mRNA and miR-218 expression was quantified in the VTA using qPCR. d–j AMPH in early adolescence downregulated Dcc expression in males, but not females (d) and increased miR-218 only in males (e) (Table 1A, B). In early adolescence, VTA miR-218 and Dcc mRNA levels correlated negatively in male, (f) but not female mice (g) (Table 1C, D). h Timeline of experiments in mid-adolescence. Male and female mice were exposed to the same recreational-like AMPH regimen, but from P35 ± 1 to P44 ± 1 and VTA transcripts were quantified one week later. i–l In mid-adolescence, AMPH no longer altered Dcc mRNA in males but downregulated levels in females (i), and it did not significantly alter miR-218 expression in either group (j) (Table 1E, F). In mid-adolescence, VTA miR-218 and Dcc mRNA levels did not correlate in males (k) but were negatively correlated in females (l) (Table 1G, H). All bar graphs are presented as mean values ± SEM, and were normalized to the saline condition in female mice (d, e, i, j). Source data are provided as a Source Data file. *p < 0.05.