The paradoxical therapeutic actions of psychostimulant drugs in people with attention deficit and hyperactivity disorder (ADHD) are still mysterious. This week, Tanaka et al. shed some light on this question in mice lacking Adcyap1, the gene that encodes PACAP (pituitary adenylate cyclase-activating polypeptide). These mice are hyperlocomotive and have deficits in prepulse inhibition (PPI), a measure of sensorimotor gating in which a weak acoustic stimulus reduces the subsequent reaction to a startling stimulus. In the Adcyap1??'/??' mouse, amphetamine normalized PPI responses and diminished hyperlocomotive behavior. Although the dopamine receptor antagonist haloperidol had no effect on PPI, a 5-HT1A receptor antagonist blocked the antihyperkinetic effect of amphetamine. There also was an amphetamine-induced increase in activity in prefrontal cortex as measured by c-Fos labeling. Although not quite an animal model of ADHD, the Adcyap1??'/??' mouse may help explain the antihyperkinetic effect of psychostimulants.
Kazuhiro Tanaka, Norihito Shintani, Hitoshi Hashimoto, Naofumi Kawagishi, Yukio Ago, Toshio Matsuda, Ryota Hashimoto, Hiroshi Kunugi, Akiko Yamamoto, Chihiro Kawaguchi, Takeshi Shimada, and Akemichi Baba
Highlights from The Journal of Neuroscience
Contact: Sara Harris
Society for Neuroscience
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