Regional distribution of pituitary adenylate cyclase activating polypeptide (PACAP) in the rat central nervous system as determined by sandwich-enzyme immunoassay

Masuo, Yoshinori; Suzuki, Nobuhiro; Matsumoto, Hirokazu; Tokito, Fumino; Matsumoto, Yoshio; Tsuda, Masao; Fujino, Masahiko

doi:10.1016/0006-8993(93)90241-e

Cited by 154 publications

(78 citation statements)

References 31 publications

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“…Histochemical studies have shown that PACAP immunoreactivity is present in several brain regions involved in the DA and 5-HT systems, including the cerebral cortex, nucleus accumbens, amygdala, hypothalamus, substantia nigra, ventral tegmental area, and dorsal raphe nucleus (Masuo et al, 1993;Piggins et al, 1996). PAC 1 receptors are expressed broadly in both the target areas and nuclei of origin of these monoaminergic systems (Hashimoto et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Psychostimulant-Induced Attenuation of Hyperactivity and Prepulse Inhibition Deficits inAdcyap1-Deficient Mice

Tanaka

Shintani²,

Hashimoto³

et al. 2006

J. Neurosci.

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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 Ϫ / Ϫ ) display psychomotor abnormalities, including increased novelty-seeking behavior and hyperactivity. In this study, Adcyap1Ϫ / Ϫ 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 Ϫ / Ϫ 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 Ϫ / Ϫ 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 Adcyap1Ϫ / Ϫ 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.

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Section: Discussionmentioning

confidence: 99%

Psychostimulant-Induced Attenuation of Hyperactivity and Prepulse Inhibition Deficits inAdcyap1-Deficient Mice

Tanaka

Shintani²,

Hashimoto³

et al. 2006

J. Neurosci.

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“…PACAP and its receptors are actively expressed in the hypothalamus, which plays a pivotal role in the control of appetite and energy homeostasis (Masuo et al, 1993;Usdin et al, 1994;Hannibal et al, 1995;Sheward et al, 1995;Piggins et al, 1996;Shioda et al, 1997). In fact, it has been previously shown that intracerebroventricular (i.c.v.)…”

Section: Introductionmentioning

confidence: 99%

Pituitary Adenylate Cyclase-Activating Polypeptide Inhibits Food Intake in Mice Through Activation of the Hypothalamic Melanocortin System

Mounien

Rego

Bizet

et al. 2008

Neuropsychopharmacol

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Pituitary adenylate cyclase-activating polypeptide (PACAP) and the proopiomelanocortin (POMC)-derived peptide, a-melanocytestimulating hormone (a-MSH), exert anorexigenic activities. While a-MSH is known to inhibit food intake and stimulate catabolism via activation of the central melanocortin-receptor MC4-R, little is known regarding the mechanism by which PACAP inhibits food consumption. We have recently found that, in the arcuate nucleus of the hypothalamus, a high proportion of POMC neurons express PACAP receptors. This observation led us to investigate whether PACAP may inhibit food intake through a POMC-dependent mechanism. In mice deprived of food for 18 h, intracerebroventricular administration of PACAP significantly reduced food intake after 30 min, and this effect was reversed by the PACAP antagonist PACAP6-38. In contrast, vasoactive intestinal polypeptide did not affect feeding behavior. Pretreatment with the MC3-R/MC4-R antagonist SHU9119 significantly reduced the effect of PACAP on food consumption. Central administration of PACAP induced c-Fos mRNA expression and increased the proportion of POMC neuronexpressing c-Fos mRNA in the arcuate nucleus. Furthermore, PACAP provoked an increase in POMC and MC4-R mRNA expression in the hypothalamus, while MC3-R mRNA level was not affected. POMC mRNA level in the arcuate nucleus of PACAP-specific receptor (PAC1-R) knock-out mice was reduced as compared with wild-type animals. Finally, i.c.v. injection of PACAP provoked a significant increase in plasma glucose level. Altogether, these results indicate that PACAP, acting through PAC1-R, may inhibit food intake via a melanocortin-dependent pathway. These data also suggest a central action of PACAP in the control of glucose metabolism.

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“…PACAP stimulates several different signaling cascades in neurons, leading to the activation of adenylate cyclase, phospholipase C, and mitogen-activated protein kinase and the mobilization of calcium (1,2,6). Histochemical studies have shown that PACAP immunoreactivity is observed in several brain regions, including the dopamine (DA) and serotonin (5-HT) systems, with high concentrations found in the nucleus accumbens, hypothalamus, amygdala, substantia nigra, and dorsal raphe (7)(8)(9). PAC 1 receptor also is expressed throughout the target areas of both the mesocorticolimbic and nigrostriatal DA systems as well as 5-HT system (10).…”

mentioning

confidence: 99%

Altered psychomotor behaviors in mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP)

Hashimoto

Shintani²,

Tanaka³

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

364

298

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Pituitary adenylate cyclase-activating polypeptide (PACAP) has been conserved remarkably during evolution and is widely expressed in the mammalian brain. In Drosophila, mutation of the PACAP homologue results in behavioral defects, including impaired olfaction-associated learning and changes in ethanol sensitivity. Here, we report the generation of mice lacking the PACAP gene (PACAP ؊/؊ ). PACAP ؊/؊ mice were born in the expected Mendelian ratios but had a high early-mortality rate. The surviving adult PACAP ؊/؊ mice displayed remarkable behavioral changes; they exhibited hyperactive and explosive jumping behaviors in an open field, increased exploratory behavior, and less anxiety in the elevated plus maze, emergence, and novel-object tests. Analysis of PACAP ؊/؊ mice brains revealed that the serotonin metabolite 5-hydroxyindoleacetic acid was slightly decreased in the cortex and striatum compared with wild-type mice. The present study provides evidence that PACAP plays a previously uncharacterized role in the regulation of psychomotor behaviors. P ituitary adenylate cyclase-activating polypeptide (PACAP) is a member of the vasoactive intestinal peptide (VIP)͞ secretin͞glucagon family of peptides and exists in two amidated forms, PACAP38 and PACAP27, that share an identical 27-aa N terminus and are alternatively processed from a 176-aa precursor called preproPACAP (1, 2). The primary structure of PACAP38 has been conserved significantly during evolution from protochordates to mammals, suggesting that the peptide exerts important activities throughout the vertebrate phylum (1, 2). In Drosophila, recent molecular cloning and transgenic rescue experiments in the memory-mutant amnesiac, which has behavioral defects that include impaired olfaction-associated learning and changes in ethanol sensitivity, demonstrated that the amnesiac gene encodes a neuropeptide homologous to vertebrate PACAP (3, 4). In addition, mammalian PACAP activated both the cAMP and Ras͞Raf signal-transduction pathways in Drosophila neurons, suggesting a neuromodulatory role of amnesiac (Drosophila PACAP) in specific neuronal populations (5). In mammals, PACAP occurs in neuronal elements, where it acts as a pleiotropic neuropeptide via three heptahelical G protein-linked receptors-one PACAP-specific (PAC 1 ) receptor and two receptors that it shares with VIP (VPAC 1 and VPAC 2 ). PACAP stimulates several different signaling cascades in neurons, leading to the activation of adenylate cyclase, phospholipase C, and mitogen-activated protein kinase and the mobilization of calcium (1, 2, 6). Histochemical studies have shown that PACAP immunoreactivity is observed in several brain regions, including the dopamine (DA) and serotonin (5-HT) systems, with high concentrations found in the nucleus accumbens, hypothalamus, amygdala, substantia nigra, and dorsal raphe (7-9). PAC 1 receptor also is expressed throughout the target areas of both the mesocorticolimbic and nigrostriatal DA systems as well as 5-HT system (10). In addition, VPAC 1 and VPAC 2 recepto...

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Regional distribution of pituitary adenylate cyclase activating polypeptide (PACAP) in the rat central nervous system as determined by sandwich-enzyme immunoassay

Cited by 154 publications

References 31 publications

Psychostimulant-Induced Attenuation of Hyperactivity and Prepulse Inhibition Deficits inAdcyap1-Deficient Mice

Psychostimulant-Induced Attenuation of Hyperactivity and Prepulse Inhibition Deficits inAdcyap1-Deficient Mice

Pituitary Adenylate Cyclase-Activating Polypeptide Inhibits Food Intake in Mice Through Activation of the Hypothalamic Melanocortin System

Altered psychomotor behaviors in mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP)

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