Neonatal DSP-4 treatment modifies GABAergic neurotransmission in the prefrontal cortex of adult rats.
N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) is a noradrenergic neurotoxin which selectively damages noradrenergic projections originating from the locus coeruleus (LC). DSP-4 treatment of rats on the first and third days after birth produces a long-lasting lesion of noradrenergic neurons in the prefrontal cortex (PFC). In DSP-4-lesioned rats, studied as adults, we observed a decrease in norepinephrine content, with no significant change in the levels of dopamine, 5-hydroxytryptamine, and gamma-aminobutyric acid (GABA). There is now a well established interaction between noradrenergic and GABAergic systems, whereby the noradrenergic system is involved in the regulation of basal GABA release, while GABAergic neurons simultaneously exert tonic inhibitory regulation of LC norepinephrine neurons. We examined GABAergic neurotransmission in the norepinephrine-denervated PFC for a better appreciation of the interaction between these two systems. Treatment with the GABA transaminase inhibitor vigabatrine (VGB) increased the GABA level of PFC (tissue content) in both intact and lesioned groups. Additionally, VGB increased extracellular GABA concentration in the PFC in both control and DSP-4-lesioned animals, but the elevation of GABA was 2-fold higher in DSP-4 lesioned rats. These findings indicate that neonatal DSP-4 treatment increases GABAergic neurotransmission in the PFC of rats in adulthood, perhaps by decreasing reactivity of central GABA(A) receptors.
Bortel
Aleksandra
A
Department of Pharmacology, Medical University of Silesia, Jordana 38 St., 41-808 Zabrze, Poland. alexandra.bortel@mcgill.ca
Nowak
Przemyslaw
P
Brus
Ryszard
R
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001596:Benzylamines / Q000633:toxicity*; D018682:GABA Agents / Q000494:pharmacology; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D017551:Microdialysis / Q000379:methods; D009498:Neurotoxins / Q000633:toxicity*; D009638:Norepinephrine / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D020888:Vigabatrin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D001596:Benzylamines; D018682:GABA Agents; D009498:Neurotoxins; D008734:Methoxyhydroxyphenylglycol; D005680:gamma-Aminobutyric Acid; D020888:Vigabatrin; C012102:DSP 4; D009638:Norepinephrine