Methamphetamine-induced hyperactivity and behavioral sensitization in PACAP deficient mice.
Mice lacking the PACAP gene (PACAP(-/-)) display psychomotor abnormalities such as novelty-induced hyperactivity and jumping behavior, and they show different responses to amphetamine, a typical psychostimulant. The present study examined the possible role of endogenous PACAP in methamphetamine (METH)-induced hyperactivity and behavioral sensitization. The locomotor activity of hyperactive PACAP(-/-) mice was measured using the infrared photocell beam detection system, Acti-Track, after a habituation period. Single administration of METH (1 and 2mg/kg) caused a robust increase in locomotor activity of mice, but this effect did not differ between wild-type and PACAP(-/-) mice. Repeated administration of METH (1mg/kg) for 7 days enhanced METH-induced hyperactivity, and this sensitization was observed even when withdrawn for 7 days. There was no difference in the degree of development and expression of METH-induced behavioral sensitization between wild-type and PACAP(-/-) mice. In addition, there was no difference in METH-induced increases in extracellular serotonin and dopamine levels in the prefrontal cortex of the normal and sensitized mice between the two groups. These results suggest that endogenous PACAP is not involved in the locomotor stimulant activity of acute METH and repeated METH-induced behavioral and neurochemical sensitization.
Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
Harumi
H
Fujii
Toshihiro
T
Ishihama
Yukio
Y
Ago
Norihito
N
Shintani
Michiya
M
Kakuda
Hitoshi
H
Hashimoto
Akemichi
A
Baba
Toshio
T
Matsuda
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D005260:Female; D005838:Genotype; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013997:Time Factors
D000697:Central Nervous System Stimulants; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012701:Serotonin; D008694:Methamphetamine; D004298:Dopamine