Prenatal daytime cocaine exposure dose-dependently alters expression of genes involved in neurotransmission (A) circadian system (B, C) growth (D) and melatonin signaling (E), and these effects are counteracted by melatonin. (A–E) Melatonin (100 nM for 45 min), Low (0.3 μM) or High (30 μM) cocaine doses (15 min), with or without melatonin pre-treatment (100 nM, 30 min). (F) Melatonin receptor antagonist Luzindole attenuates the counteracting effects of melatonin on cocaine-induced changes in the expression of all six melatonin receptor genes; only one (zMel1a-1) receptor shown. Treatments: luzindole 50 µM for 20 min prior to melatonin; melatonin 100 nM for 20 min prior to cocaine; cocaine 0.3 µM for 15 min. (G) Dose-dependent effects of cocaine (20 min) on melatonin receptor expression. Y axis: fold change relative to control (=1). N=3–4 samples/treatment group, 25 embryos/sample. Mean±SEM, t-test (vs. control), * p<0.05, ** p<0.01, *** p<0.001; One way ANOVA (between treatments), a: p<0.05, vs. cocaine-only group. Mlt-melatonin; Coc-cocaine.
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