title: Impact of early life stress on the reinforcing and behavioral-stimulant effects of psychostimulants in rhesus monkeys.
abstract: Early life stress has effects on behavior and stress reactivity, which are linked to enhanced sensitivity to stimulants in rodents. This study investigated whether rhesus monkeys that experienced early life stress would show altered sensitivity to the reinforcing effects of stimulants as compared with controls. Control (n=5) and maternally separated (n=4) monkeys were trained to self-administer cocaine (0.1 mg/kg/injection) under a second-order schedule of intravenous drug delivery. The rate of acquisition and subsequent dose-effect determinations for cocaine (0.01-1.0 mg/kg/injection) and amphetamine (0.003-0.3 mg/kg/injection) provided complementary measures of reinforcing effectiveness. In addition, stimulant-induced increases in home cage activity and dopamine D2 receptor binding potential were quantified with positron emission tomography neuroimaging. Compared with controls, maternally separated monkeys showed lower responding during the acquisition of self-administration and in the dose-response curves for both stimulants, and significantly lower response rates during maintenance of cocaine self-administration. Maternally separated monkeys also failed to exhibit stimulant-induced increases in motor activity. Groups did not differ in dopamine D2 receptor binding potential in the caudate nucleus or the putamen. Taken together, the results of this study do not provide support for early life stress leading to enhanced vulnerability to stimulant use in the nonhuman primate model employed.
authors.affiliation: Yerkes National Primate Research Center bDepartment of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia 30329, USA.
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Ewing Corcoran
authors.forename: Leonard L
authors.initials: LL
authors.lastname: Howell
mesh_terms: D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001549:Benzamides / Q000032:analysis; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D008253:Macaca mulatta; D008426:Maternal Deprivation; D009043:Motor Activity / Q000187:drug effects; D049268:Positron-Emission Tomography; D011699:Putamen / Q000000981:diagnostic imaging / Q000378:metabolism; D011759:Pyrrolidines / Q000032:analysis; D011869:Radioligand Assay; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012646:Self Administration; D013315:Stress, Psychological / Q000523:psychology*
chemical_list: D001549:Benzamides; D000697:Central Nervous System Stimulants; C094948:N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D000661:Amphetamine; D003042:Cocaine