Effects of chronic treatment with trihexyphenidyl and carbamazepine alone or in combination with haloperidol on substance P content in rat brain: a possible implication of substance P in affective disorders.
To assess the roles of substance P in neurologic or psychiatric illnesses, effects of acute or chronic (40- or 80-day dietary) treatment with trihexyphenidyl and carbamazepine alone or in combination with haloperidol on substance P content were investigated in the rat brain. Either acute or chronic trihexyphenidyl administration did not alter substance P content when administered alone and did not prevent the haloperidol-induced substance P decrease in the striatum and substantia nigra when coadministered with haloperidol. Chronic dietary carbamazepine administration dose-dependently increased substance P content in the striatum and substantia nigra, but not in the raphe area, in a haloperidol-reversible manner. Carbamazepine also dose-dependently increased gamma-aminobutyric acid levels in the substantia nigra without altering the striatal dopamine turnover rate. The lack of effect of trihexyphenidyl, an anticholinergic drug used to treat antipsychotic drug-induced extrapyramidal (Parkinson) syndromes, suggests that antipsychotic drug-induced reduction in substance P content is not involved in the extrapyramidal side effects. Since the effects of carbamazepine on substance P content are identical with previously described effects of lithium, an alteration in substance P neurotransmission may be one of the neurochemical bases of common clinical and behavioral effects of carbamazepine and lithium on affective disorders.
Mitsushio
H
H
Division of Mental Disorder Research, National Center of Neurology and Psychiatry, Tokyo, Japan.
Takashima
M
M
Mataga
N
N
Toru
M
M
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002220:Carbamazepine / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005971:Glutamates / Q000032:analysis; D018698:Glutamic Acid; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology*; D008094:Lithium / Q000494:pharmacology; D008297:Male; D019964:Mood Disorders / Q000209:etiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D013373:Substance P / Q000032:analysis*; D014282:Trihexyphenidyl / Q000008:administration & dosage / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000032:analysis
D005971:Glutamates; D012701:Serotonin; D013373:Substance P; D002220:Carbamazepine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D014282:Trihexyphenidyl; D008094:Lithium; D006220:Haloperidol; D004298:Dopamine