Pituitary Adenylate Cyclase-Activating Polypeptide Disrupts Motivation, Social Interaction, and Attention in Male Sprague Dawley Rats

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• 作者：Rachel J. Donahue^a ; Archana Venkataraman^a ; F. Ivy Carroll^b ; Edward G. Meloni^a ; William A. Carlezon Jr.^a ; ^{bcarlezon@mclean.harvard.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Anhedonia ; Attention ; Model ; Pituitary adenylate cyclase&ndash ; activating peptide (PACAP) ; Rat ; Social interaction
• 刊名：Biological Psychiatry
• 出版年：2016
• 出版时间：15 December 2016
• 年：2016
• 卷：80
• 期：12
• 页码：955-964
• 全文大小：962 K

文摘

Severe or prolonged stress can trigger psychiatric illnesses including mood and anxiety disorders. Recent work indicates that pituitary adenylate cyclase–activating polypeptide (PACAP) plays an important role in regulating stress effects. In rodents, exogenous PACAP administration can produce persistent elevations in the acoustic startle response, which may reflect anxiety-like signs including hypervigilance. We investigated whether PACAP causes acute or persistent alterations in behaviors that reflect other core features of mood and anxiety disorders (motivation, social interaction, and attention).

Methods

Using male Sprague Dawley rats, we examined if PACAP (.25–1.0 µg, intracerebroventricular infusion) affects motivation as measured in the intracranial self-stimulation test. We also examined if PACAP alters interactions with a conspecific in the social interaction test. Finally, we examined if PACAP affects performance in the 5-choice serial reaction time task, which quantifies attention and error processing.

Results

Dose-dependent disruptions in motivation, social interaction, and attention were produced by PACAP, as reflected by increases in reward thresholds, decreases in social behaviors, and decreases in correct responses and alterations in posterror accuracy. Behavior normalized quickly in the intracranial self-stimulation and 5-choice serial reaction time task tests but remained dysregulated in the social interaction test. Effects on attention were attenuated by the corticotropin-releasing factor receptor-1 antagonist antalarmin but not the κ opioid receptor antagonist JDTic.

Conclusions

Our findings suggest that PACAP affects numerous domains often dysregulated in mood and anxiety disorders, but that individual signs depend on brain substrates that are at least partially independent. This work may help to devise therapeutics that mitigate specific signs of these disorders.