Fig. 4: Recreational AMPH in adolescence induces ectopic growth of mesolimbic dopamine axons to the PFC in male mice. | Nature Communications

Fig. 4: Recreational AMPH in adolescence induces ectopic growth of mesolimbic dopamine axons to the PFC in male mice.

From: Amphetamine disrupts dopamine axon growth in adolescence by a sex-specific mechanism in mice

Fig. 4

a Experimental design. b Photomicrographs showing the prelimbic PFC (PrL) of adult mice injected with tracer viruses in adolescence. Top Dopamine axons continued to grow from the NAc to the PFC in adolescence in the saline condition (closed arrowheads). Bottom The number of axons that grew to the PFC in adolescence is dramatically increased in adult mice that were exposed to AMPH early in adolescence. c Stereological quantification reveals a significant increase in fluorescent axon terminals across the cingulate 1 (Cg1), PrL, and infralimbic (IL) subregions of the medial PFC and a pronounced dorsal-to-ventral gradient (Table 4A), paired with a significant decrease of fluorescent terminals in the NAc (d, Table 4B). e The number of labeled terminals in the PFC and in the NAc are negatively correlated (Table 4C). f The percentage of VTA dopamine neuron infection is similar between treatment groups (Table 4D). g Exposure to AMPH induces robust conditioned place preference (CPP) (Table 1E). This is not the case in male mice exposed to a therapeutic-like amphetamine regimen (ALD, 0.5 mg/kg). h Experimental design. i Photomicrographs showing the PrL of adult mice injected with tracer viruses in adolescence. The number of labeled axons that continued to grow from the NAc to the PFC in adolescence (closed arrowheads) is not different between adult mice that were exposed to saline (Top) or to ALD in adolescence (Bottom). ALD in adolescence does not alter the number of labeled dopamine terminals in the PFC (j, Table 1F) or the in the NAc (k, Table 1G), indicating that this AMPH dose does not interfere with dopamine axon targeting. All bar graphs are presented as mean values ± SEM. Box plots include a box extending from the 25th to 75th percentiles, with the median indicated by a line and with whiskers extending from the minima to the maxima. Source data are provided as a Source Data file. *p < 0.05, **p < 0.01, ***p < 0.01.

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