Phorbol ester differentiates the levels of [3H]MK-801 binding in rats lines selected for differential sensitivity to the hypnotic effects of ethanol.
These studies addressed the possible involvement between sensitivity to the hypnotic action of ethanol and function of the NMDA receptor. The studies were carried out using high-alcohol sensitive (HAS) and low-alcohol sensitive (LAS) rats, two rats having differential sensitivity to the acute hypnotic action of ethanol. The animal models were developed by a selective breeding experiment. Using a quantitative autoradiograph technique, it was demonstrated that [3H]MK-801 binding to the NMDA receptor was highest in hippocampus in both HAS and LAS rats, but significant [3H]MK-801 binding was also detected in cortex, caudate-putamen, and thalamus of HAS and LAS rats. The density of [3H]MK-801 binding was lower only in cerebellar granule layers of untreated HAS rats as compared to the same brain area in untreated LAS rats. Activation of protein kinase C (PKC) by 100 nM PDBu, increased [3H]MK-801 binding in cortex, caudate-putamen, thalamus, central gray, and cerebellum of HAS rats but activation of PKC did not influence [3H]MK-801 binding in LAS rats. These activation of PKC differentiates between [3H]MK-801 binding of HAS and LAS rats in frontal cortex (layer II-IV and cingulate), caudate-putamen, and ventral lateral thalamic nuclei. The basal level of PKC-gamma mRNA was higher in HAS rats than that of LAS rats. These results suggest that the activation of PKC potentiates NMDA receptor function of the rat line which is more sensitive to alcohol (HAS) but does not affect [3H]MK-801 binding of alcohol resistant (LAS) rats.
Oh
Seikwan
S
Department of Neuroscoence, College of Medicine and Medical Science Institute, Ewha University, Seoul 157-710, Korea. skoh@ewha.ac.kr
Chang
Chia-Yu
CY
Baker
Rodney C
RC
Ho
Ing K
IK
D000818:Animals; D001345:Autoradiography; D001923:Brain Chemistry / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism*; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007090:Image Interpretation, Computer-Assisted; D017403:In Situ Hybridization; D008297:Male; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D010703:Phorbol Esters / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D002492:Central Nervous System Depressants; D018691:Excitatory Amino Acid Antagonists; D006993:Hypnotics and Sedatives; D010703:Phorbol Esters; D012333:RNA, Messenger; D015240:Phorbol 12,13-Dibutyrate; D000431:Ethanol; D016291:Dizocilpine Maleate; C087857:protein kinase C gamma; D011493:Protein Kinase C