| First Author | Tanaka K | Year | 2006 |
| Journal | J Neurosci | Volume | 26 |
| Issue | 19 | Pages | 5091-7 |
| PubMed ID | 16687500 | Mgi Jnum | J:108629 |
| Mgi Id | MGI:3624451 | Doi | 10.1523/JNEUROSCI.4376-05.2006 |
| Citation | Tanaka K, et al. (2006) Psychostimulant-induced attenuation of hyperactivity and prepulse inhibition deficits in Adcyap1-deficient mice. J Neurosci 26(19):5091-7 |
| abstractText | Psychostimulants, including amphetamine, act as antihyperkinetic agents in humans with hyperkinetic disorder such as attention-deficit hyperactivity disorder and are known to be effective in enhancing attention-related processes; however, the underlying mechanisms have not been adequately addressed. Mice lacking the Adcyap1 gene encoding the neuropeptide pituitary adenylate cyclase-activating polypeptide (Adcyap1(-/-)) display psychomotor abnormalities, including increased novelty-seeking behavior and hyperactivity. In this study, Adcyap1(-/-) mice showed sensory-motor gating deficits, measured as deficits in prepulse inhibition (PPI), and showed normal PPI in response to amphetamine. Amphetamine also significantly decreased hyperlocomotion in Adcyap1(-/-) mice, and this paradoxical antihyperkinetic effect depended on serotonin 1A (5-HT(1A)) receptor signaling. c-Fos-positive neurons were increased in the prefrontal cortex in amphetamine-treated Adcyap1(-/-) mice, suggesting increased inhibitory control by prefrontal neurons. Additionally, amphetamine produced an antihyperkinetic effect in wild-type mice that received the 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino)tetralin. These results indicate that Adcyap1(-/-) mice act as a model of hyperlocomotion and PPI deficits and suggest that 5-HT(1A)-mediated pathways are important determinants of the psychostimulant-elicited, rate-dependent effects that are in a negative function of the baseline rate of activity. |
