C-FOS ANTISENSE REDUCES EXPRESSION OF KROX-24 IN RAT CAUDATE AND NEOCORTEX

1. The aim of this study was to investigate the neurochemical effects and measure the anatomical spread of infusion of c-fos antisense (AS) DNA into the striatum. 2. Rats were anesthetized and infused in opposi ng striata with c-fos AS and c-fos sense (S) DNA. Ten hours later they were injected with apomorphine (2 mg/kg, i.p.) and 20 min later they were overdosed with sodium pentobarbital and their brains either perfu sed or frozen. Vibratome-cut sections were immunostained for the detec tion of c-fos, JunB, Krox 24, somatostatin, substance P, dynorphin, ty rosine hydroxylase, and enkephalin. Cryostat-cut sections from the cau date were immunostained for the detection of c-fos, JunB, and Krox 24, as well as in situ hybridization for proenkephalin mRNA. Sections fro m the globus pallidus were used for the autoradiographic localization of D2 dopamine and A2(a), adenosine receptors, Sections from the subst antia nigra were used for the autoradiographic localization of D1 dopa mine and cannabinoid receptors, A second group of rats was injected in opposing striata with biotin-labeled c-fos AS DNA and c-fos S DNA. Te n hours later they were challenged with apomorphine (2 mg/kg, i.p.) an d 20 min later brains were either perfused or frozen, Sections from th ese brains were cut throughout the rostral-caudal extent of the forebr ain and the biotin labeled AS DNA was localized. 3. Krox 24 was expres sed at high levels on the sense side of the brain in the striatum and overlying neocortex, However, on the AS-injected side there was a redu ction in Krox 24 expression in striatum and overlying cortex. The biot in-labeled AS studies confirmed that the striatal infusion spread thro ughout the dorsal striatum as well as the overlying neocortex. We did npt detect any changes in neurotransmitter receptors, neuropeptides, o r tyrosine hydroxylase in AS/S-injected rat brains. 4. These results d emonstrate that c-fos AS reduces Krox 24 expression in striatal and ne ocortical neurons but does not change the expression of a number of ot her proteins involved in basal ganglia function. Whether this effect i s due to nonspecific actions of c-fos AS or to its effects on a compon ent of the transduction pathway responsible for basal Krox 24 expressi on (NMDA receptors?) is unknown.