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Acute and chronic effects of gamma-butyrolactone-gamma-carbonyl-histidyl-prolinamide (DN-1417) were investigated on motor activity, dopamine (DA) metabolites and DA receptors in various brain regions of rats. The motor activity, as measured with Automex recorder, was enhanced after a single injection with DN-1417 (20 mg/kg, IP), and the motor stimulating action persisted during 21 daily injections. Acute DN-1417 elevated both homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in 7 brain regions, prefrontal cortex polar, medial and lateral fields, nucleus accumbens, olfactory tubercles, amygdala and striatum. After chronic treatment for 7 days, the acute effect of DN-1417 on DA metabolites disappeared in all regions except for the striatum in which DN-1417 still increased HVA and DOPAC. The response of striatal DA metabolites was also observed after chronic treatment for 21 days. Chronic DN-1417 produced no significant change in 3H-spiperone binding in the prefrontal cortex, nucleus accumbens, olfactory tubercles and striatum, while striatal 3H-DA binding displaced by 30 nM spiperone was enhanced after chronic treatment. These results indicate that DN-1417 interacts with mesocortical, mesolimbic and nigrostriatal DA systems in the different modes of action. The lack of tolerance to motor hyperactivity, however, raises the question as to whether DN-1417-induced hyperactivity may be mediated by the activation of mesolimbic DA neurons. The involvement of nigrostriatal neurons in DN-1417-induced motor hyperactivity is suggested.
T Nakahara, and
T Matsumoto, and
M Hirano, and
H Uchimura, and
H Yokoo, and
K Nakamura, and
K Ishibashi, and
H Hirano
January 1985,
Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica,
T Nakahara, and
T Matsumoto, and
M Hirano, and
H Uchimura, and
H Yokoo, and
K Nakamura, and
K Ishibashi, and
H Hirano
October 1983,
Japanese journal of pharmacology,
T Nakahara, and
T Matsumoto, and
M Hirano, and
H Uchimura, and
H Yokoo, and
K Nakamura, and
K Ishibashi, and
H Hirano
September 1985,
Biological psychiatry,
T Nakahara, and
T Matsumoto, and
M Hirano, and
H Uchimura, and
H Yokoo, and
K Nakamura, and
K Ishibashi, and
H Hirano
January 1992,
Epilepsia,
T Nakahara, and
T Matsumoto, and
M Hirano, and
H Uchimura, and
H Yokoo, and
K Nakamura, and
K Ishibashi, and
H Hirano
January 1983,
The Kurume medical journal,
T Nakahara, and
T Matsumoto, and
M Hirano, and
H Uchimura, and
H Yokoo, and
K Nakamura, and
K Ishibashi, and
H Hirano
April 1983,
Life sciences,
T Nakahara, and
T Matsumoto, and
M Hirano, and
H Uchimura, and
H Yokoo, and
K Nakamura, and
K Ishibashi, and
H Hirano
September 1986,
Yakubutsu, seishin, kodo = Japanese journal of psychopharmacology,
T Nakahara, and
T Matsumoto, and
M Hirano, and
H Uchimura, and
H Yokoo, and
K Nakamura, and
K Ishibashi, and
H Hirano
October 1986,
International clinical psychopharmacology,
T Nakahara, and
T Matsumoto, and
M Hirano, and
H Uchimura, and
H Yokoo, and
K Nakamura, and
K Ishibashi, and
H Hirano
May 1984,
Acta endocrinologica,
T Nakahara, and
T Matsumoto, and
M Hirano, and
H Uchimura, and
H Yokoo, and
K Nakamura, and
K Ishibashi, and
H Hirano
January 1985,
Psychopharmacology,
