A new animal model for schizophrenia: interactions with adrenergic mechanisms.
Amphetamine-induced stereotyped behavior in animals is proposed as a model for schizophrenia. Chronic amphetamine administration produces stereotyped behavior and a paranoid schizophreniform syndrome in man, whereas in animals a behavioral sensitization to stereotypy is evoked. We now show that phenylethylamine (PEA), an amphetamine-like stimulant concentrated in the limbic system of human brain, produces stereotypy in rats with a behavioral sensitization when chronically administered. In comparing amphetamine-induced stereotypy with PEA-induced stereotypy, we found that the alpha-adrenergic blocking agents phentolamine and phenoxybenzamine selectively antagonize PEA stereotypy, whereas the beta-adrenergic blocking agent propranolol fails to alter significantly stereotypies evoked by PEA or amphetamine administration. Catecholamine depletion by alpha-methyl-p-tyrosine administration blocks stereotypies induced by both PEA amphetamine, whereas selective norepinephrine depletion antagonizes only PEA stereotypy; the amino acid precursors of both norepinephrine and dopamine potentiate stereotypies. Therefore, PEA-elicited stereotypy, but not amphetamine-elicited stereotypy, is dependent upon norepinephrine; the significance of this for the PEA animal model of schizophrenia is discussed.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003913:Dextroamphetamine / Q000494:pharmacology; D004195:Disease Models, Animal; D004050:Ditiocarb / Q000494:pharmacology; D004336:Drug Antagonism; D004357:Drug Synergism; D006801:Humans; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D009068:Movement / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism*; D010643:Phenoxybenzamine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011930:Reaction Time; D012559:Schizophrenia / Q000378:metabolism*
D008781:Methyltyrosines; D010643:Phenoxybenzamine; D004050:Ditiocarb; D011433:Propranolol; D003913:Dextroamphetamine; D009638:Norepinephrine; D010646:Phentolamine