title: Morphine alters the locomotor responses to a D2/D3 dopamine receptor agonist differentially in adolescent and adult mice.
abstract: The D2-like dopamine receptors mediate the emotional/aversive state during morphine withdrawal. Given age-dependent differences in the affective responses to withdrawal, this study examined whether the response to dopamine receptor agonists is altered differentially across ages following morphine administration. Adolescent and adult mice were injected with morphine (twice daily, 10-40 mg/kg, s.c.) or saline for 6 days. Subsequently, they were examined for their locomotor response to quinpirole, a D2/D3 receptor agonist, and SKF 38393, a D1 receptor agonist. Quinpirole dose-dependently reduced locomotion in drug-naïve animals. Initial suppression was also observed in morphine-treated animals, but was followed by enhanced locomotion. Notably, this enhanced locomotion was markedly greater in adolescents than adults. Quinpirole-induced hypo-locomotion is thought to be mediated by the presynaptic D2Short receptors, whereas its activating effect is mediated by postsynaptic D2Long/D3 receptors. This suggests that following morphine administration, the postsynaptic, but not the presynaptic, dopaminergic signaling is differentially modulated across ages. This locomotor supersensitivity was not observed for SKF 38393, a D1 dopamine receptor agonist. The D2/D3 receptors are involved in the pathophysiology of many mental illnesses. Thus, this study offers a potential explanation for the increased psychiatric disorder co-morbidities when drug use begins during adolescence.
authors.affiliation: Behavioral and Cellular Neuroscience, Department of Psychology, Texas A&M University, College Station, TX, USA.
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Hofford
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Wellman
authors.forename: Shoshana
authors.initials: S
authors.lastname: Eitan
mesh_terms: D000375:Aging; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006948:Hyperkinesis / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009021:Morphine Dependence / Q000188:drug therapy*; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000378:metabolism; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D019257:Quinpirole / Q000008:administration & dosage / Q000627:therapeutic use; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000819:agonists* / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D018491:Dopamine Agonists; C493594:Drd3 protein, mouse; D009419:Nerve Tissue Proteins; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D019257:Quinpirole