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The Journal of Neuroscience, November 2, 2005, 25(44):10282-10289; doi:10.1523/JNEUROSCI.2572-05.2005

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Behavioral/Systems/Cognitive
Rapid Eye Movement Sleep Is Reduced in Prolactin-Deficient Mice

Ferenc Obál, Jr,^1,2  Fabio Garcia-Garcia,¹ Balint Kacsóh,³ Ping Taishi,¹ Stewart Bohnet,¹ Nelson D. Horseman,⁴ and James M. Krueger¹

¹Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, College of Veterinary Medicine, Washington State University, Pullman, Washington 99164-6520, ²Department of Physiology, University of Szeged, A. Szent-Gyorgyi Medical Center, 6720 Szeged, Hungary, ³Division of Basic Medical Sciences and Department of Pediatrics, Mercer University School of Medicine, Macon, Georgia 31207, and ⁴Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio 45267-0576

Prolactin (PRL) is implicated in the modulation of spontaneous rapid eye movement sleep (REMS). Previous models of hypoprolactinemic animals were characterized by changes in REMS, although associated deficits made it difficult to ascribe changes in REMS to reduced PRL. In the current studies, male PRL knock-out (KO) mice were used; these mice lack functional PRL but have no known additional deficits. Spontaneous REMS was reduced in the PRL KO mice compared with wild-type or heterozygous littermates. Infusion of PRL for 11-12 d into PRL KO mice restored their REMS to that occurring in wild-type or heterozygous controls. Six hours of sleep deprivation induced a non-REMS and a REMS rebound in both PRL KO mice and heterozygous littermates, although the REMS rebound in the KOs was substantially less. Vasoactive intestinal peptide (VIP) induced REMS responses in heterozygous mice but not in KO mice. Similarly, an ether stressor failed to enhance REMS in the PRL KOs but did in heterozygous littermates. Finally, hypothalamic mRNA levels for PRL, VIP, neural nitric oxide synthase (NOS), inducible NOS, and the interferon type I receptor were similar in KO and heterozygous mice. In contrast, tyrosine hydroxylase mRNA was lower in the PRL KO mice than in heterozygous controls and was restored to control values by infusion of PRL, suggesting a functioning short-loop negative feedback regulation in PRL KO mice. Data support the notion that PRL is involved in REMS regulation.

Key words: stress; VIP; sleep deprivation; rapid eye movement; sleep; prolactin

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Received June 22, 2005; revised September 28, 2005; accepted September 28, 2005.

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