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Methamphetamine-induced hyperactivity and behavioral sensitization in PACAP deficient mice.

Harumi Fujii1, Toshihiro Ishihama, Yukio Ago

  • 1Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.

Peptides
|July 31, 2007
PubMed
Summary

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Endogenous PACAP does not influence methamphetamine (METH) effects. PACAP(-/-) mice showed no difference in METH-induced hyperactivity or sensitization compared to wild-type mice.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Genetics

Background:

  • Pituitary adenylyl cyclase-activating polypeptide (PACAP) plays a role in psychomotor behaviors.
  • Mice lacking the PACAP gene (PACAP(-/-)) exhibit abnormal psychomotor activity and altered responses to amphetamines.

Purpose of the Study:

  • To investigate the role of endogenous PACAP in methamphetamine (METH)-induced hyperactivity.
  • To examine the involvement of PACAP in METH-induced behavioral sensitization and associated neurochemical changes.

Main Methods:

  • Locomotor activity was assessed in PACAP(-/-) and wild-type mice using an infrared photocell beam detection system.
  • METH was administered acutely (1-2 mg/kg) and repeatedly (1 mg/kg for 7 days) to assess hyperactivity and sensitization.
  • Extracellular serotonin and dopamine levels in the prefrontal cortex were measured in normal and sensitized mice.

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Main Results:

  • Acute METH administration significantly increased locomotor activity in both wild-type and PACAP(-/-) mice, with no significant difference between groups.
  • Repeated METH administration induced behavioral sensitization in both genotypes, which persisted after a 7-day withdrawal period.
  • No significant differences were observed in the development or expression of METH-induced behavioral sensitization between PACAP(-/-) and wild-type mice.
  • METH-induced increases in extracellular dopamine and serotonin in the prefrontal cortex were comparable in both groups.

Conclusions:

  • Endogenous PACAP is not implicated in the acute locomotor stimulant effects of METH.
  • PACAP does not play a role in the development or expression of METH-induced behavioral sensitization.
  • The study suggests that PACAP is not involved in METH-induced neurochemical alterations in the prefrontal cortex.