title: The use-dependent, nicotinic antagonist BTMPS reduces the adverse consequences of morphine self-administration in rats in an abstinence model of drug seeking.
abstract: In this study, the use-dependent, nicotinic receptor antagonist bis (2,2,6,6-tetramethyl-4-piperidinyl) sebacate (BTMPS) was evaluated for its ability to attenuate the adverse consequences associated with morphine in rats in all three phases of an abstinence model of drug seeking: self-administration, acute withdrawal, and delayed test of drug seeking. Rats were allowed to self-administer morphine (FR1 schedule) with an active response lever, on a 24 h basis inside operant chambers, for 14 days. Each rat was subsequently evaluated for stereotypical behaviors associated with spontaneous morphine withdrawal. Rats were then placed in standard housing cages for a six week period of protracted abstinence from morphine. After this period, each rat was placed back into its respective operant chamber for a 14 day assessment of unrewarded drug seeking responses. BTMPS was administered to the animals in all three clinically relevant phases in three separate sets of experiments. BTMPS treatment during the self-administration phase resulted in up to a 34% reduction of lever responses to morphine when compared to vehicle treated control animals, as well as a 32% reduction in the dose of morphine self-administered. When given during self-administration and acute withdrawal, BTMPS treatment decreased acute withdrawal symptoms (up to 64%) of morphine use and reduced (up to 45%) drug seeking responses after six weeks of protracted withdrawal compared to control animals. BTMPS treatment after six weeks of abstinence from morphine had no effect. These results offer insight into the role of central cholinergic receptors in the onset and maintenance of drug addiction.
authors.affiliation: Department of Pharmacology and Toxicology, Alzheimer's Research Center, Medical College of Georgia, Augusta, GA 30912-2450, USA.
authors.forename: Brandon J
authors.initials: BJ
authors.lastname: Hall
authors.forename: Laura S
authors.initials: LS
authors.lastname: Pearson
authors.forename: Alvin V
authors.initials: AV
authors.lastname: Terry
authors.forename: Jerry J
authors.initials: JJ
authors.lastname: Buccafusco
mesh_terms: D000818:Animals; D016739:Behavior, Addictive / Q000188:drug therapy* / Q000523:psychology; D003652:Decanoic Acids / Q000627:therapeutic use*; D004195:Disease Models, Animal; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D009021:Morphine Dependence / Q000188:drug therapy / Q000523:psychology; D018733:Nicotinic Antagonists / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000523:psychology
chemical_list: D003652:Decanoic Acids; D018733:Nicotinic Antagonists; D010880:Piperidines; C083752:Tinuvin 770; D009020:Morphine