Evolution and Variation of Macaca 5HT1

Goldman, David

Abstract

5HT1A is the intronless coding locus (1266 base pair - 422 amino acids) for a G protein-coupled serotonin receptor with a typical 7-transmembrane structure, located on chromosome 5 in humans. Previous work in this laboratory discovered two variants (Biochem Biophys Res Commun 1995;210(2):530-6), characterized their frequency and distribution in human populations (Human Mutation 1996;7:135-43) and investigated their functional effects (Neuropsychopharmacology 1997; 17:18-26). In order to assess the polymorphic spectrum of this locus in a primate animal model heavily used in neuroscience research, we have cloned and sequenced the highly conserved 5HT1A gene from four macaque species (Macaca fascicularis , Macaca maura, Macaca mulatta and Macaca nemestrina) and from the vervet monkey (Cercopithecus aethiops). Both interspecific and intraspecific sequence variations have been discovered, the interspecific variation supporting the known phylogeny of Macaca, while the intraspecific variation will be characterized in a large group of Macaca mulatta for which serotonin metabolites and behavioral data exist in order to assess potential association between serotonin receptor variants and behavior.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Type: Intramural Research (Z01)
• Project #: 1Z01AA000294-02
• Application #: 6097598
• Study Section: Special Emphasis Panel (LNG)
• Support Year: 2
• Fiscal Year: 1998

Institution

• Name: National Institute on Alcohol Abuse and Alcoholism
• Country: United States

Publications

Barr, Christina S; Dvoskin, Rachel L; Yuan, Qiaoping et al. (2008) CRH haplotype as a factor influencing cerebrospinal fluid levels of corticotropin-releasing hormone, hypothalamic-pituitary-adrenal axis activity, temperament, and alcohol consumption in rhesus macaques. Arch Gen Psychiatry 65:934-44

Barr, Christina S; Schwandt, Melanie L; Lindell, Stephen G et al. (2008) Variation at the mu-opioid receptor gene (OPRM1) influences attachment behavior in infant primates. Proc Natl Acad Sci U S A 105:5277-81

Spinelli, Simona; Schwandt, Melanie L; Lindell, Stephen G et al. (2007) Association between the recombinant human serotonin transporter linked promoter region polymorphism and behavior in rhesus macaques during a separation paradigm. Dev Psychopathol 19:977-87

Barr, Christina S; Schwandt, Melanie; Lindell, Stephen G et al. (2007) Association of a functional polymorphism in the mu-opioid receptor gene with alcohol response and consumption in male rhesus macaques. Arch Gen Psychiatry 64:369-76

Lorenz, Joseph G; Long, Jeffrey C; Linnoila, Markku et al. (2006) Genetic and other contributions to alcohol intake in rhesus macaques (Macaca mulatta). Alcohol Clin Exp Res 30:389-98

Barr, Christina S; Goldman, David (2006) Non-human primate models of inheritance vulnerability to alcohol use disorders. Addict Biol 11:374-85

Goldman, David; Oroszi, Gabor; Ducci, Francesca (2005) The genetics of addictions: uncovering the genes. Nat Rev Genet 6:521-32

Barr, Christina S; Newman, Timothy K; Lindell, Stephen et al. (2004) Interaction between serotonin transporter gene variation and rearing condition in alcohol preference and consumption in female primates. Arch Gen Psychiatry 61:1146-52

Barr, Christina S; Newman, Timothy K; Schwandt, Melanie et al. (2004) Sexual dichotomy of an interaction between early adversity and the serotonin transporter gene promoter variant in rhesus macaques. Proc Natl Acad Sci U S A 101:12358-63

Barr, Christina S; Newman, Timothy K; Shannon, Courtney et al. (2004) Rearing condition and rh5-HTTLPR interact to influence limbic-hypothalamic-pituitary-adrenal axis response to stress in infant macaques. Biol Psychiatry 55:733-8