Effects of prenatal cocaine exposure on haloperidol-induced increases in prolactin release and dopamine turnover in weanling, periadolescent, and adult offspring.
Offspring of dams given 40 mg/kg cocaine SC on gestational days (GD) 8-20 (E8-20) (C40), dams given 0.9% saline SC on E8-20 that were pair fed and watered to C40 dams (PF), and untreated control dams given ad lib access to food and water (LC) were challenged with haloperidol (0.0, 0.05, 0.10, or 0.50 mg/kg) at either 21, 35, or 60 days postnatally (P21, 35, 60). One hour postinjection, animals were sacrificed, trunk blood collected for assay of prolactin, and the striatum (ST) and nucleus accumbens (NAc) removed. The ratio of the dopamine metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid to dopamine (DA) as well as the ratio of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) to serotonin (5-HT) were determined in these brain regions as an index of DA and 5-HT turnover, respectively. Assessment of 5-HIAA/5-HT ratios did not indicate any reliable dose or prenatal treatment effects. Reminiscent of previous findings obtained in C40 offspring at P11 (35), P21 C40 offspring exhibited a slightly reduced sensitivity to haloperidol relative to LC controls both in terms of DA ratios in the NAc as well as plasma prolactin levels. These findings were also evident in PF controls suggesting that they may be the result of prenatal undernutrition. Furthermore, this reduced sensitivity was not evident at the older test ages. At P60, planned comparisons revealed haloperidol-induced increases in prolactin levels in C40 males but not PF or LC males; these findings could potentially reflect feminization in males following prenatal cocaine exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
Goodwin, GA; Rajachandran, L; Moody, CA; Francis, R; Kuhn, CM; Spear, LP
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