| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 4338510 | Neuroscience | 2012 | 10 Pages |
Current therapies for attention deficit hyperactivity disorder (ADHD) have varying efficacy in individuals with fetal alcohol spectrum disorders (FASD), suggesting that alternative therapeutics are needed. Developmental exposure to ethanol produces changes in dopamine (DA) systems, and DA has also been implicated in ADHD pathology. In the current study, lobeline, which interacts with proteins in dopaminergic presynaptic terminals, was evaluated for its ability to attenuate neonatal ethanol-induced locomotor hyperactivity and alterations in dopamine transporter (DAT) function in striatum and prefrontal cortex (PFC). From postnatal days (PND) 1–7, male and female rat pups were intubated twice daily with either 3 g/kg ethanol or milk, or were not intubated (non-intubated control) as a model for “third trimester” ethanol exposure. On PND 21 and 22, pups received acute lobeline (0, 0.3, 1, or 3 mg/kg), and locomotor activity was assessed. On PND 23–25, pups again received an acute injection of lobeline (1 or 3 mg/kg), and DAT kinetic parameters (Km and Vmax) were determined. Results demonstrated that neonatal ethanol produced locomotor hyperactivity on PND 21 that was reversed by lobeline (1 and 3 mg/kg). Although striatal DAT function was not altered by neonatal ethanol or acute lobeline, neonatal ethanol exposure increased the Vmax for DAT in the PFC, suggesting an increase in DAT function in PFC. Lobeline ameliorated this effect on PFC Vmax at the same doses that decreased hyperactivity. Methylphenidate, the gold standard therapeutic for ADHD, was also evaluated for comparison with lobeline. Methylphenidate decreased DAT Vmax and Km in PFC from ethanol-treated pups. Thus, lobeline and methylphenidate differentially altered DAT function following neonatal ethanol exposure. Collectively, these findings provide support that lobeline may be a useful pharmacotherapy for some of the deficits associated with neonatal ethanol exposure.
▶Lobeline attenuation of neonatal ethanol-induced hyperactivity is evaluated. ▶Lobeline effects on brain dopamine transporter in ethanol-treated rats are evaluated. ▶Lobeline reversed neonatal ethanol effect on hyperactivity. ▶Lobeline attenuated neonatal ethanol effects in prefrontal cortex. ▶Lobeline may be a useful for deficits associated with neonatal ethanol exposure.
