title: Relationship between central behavioral effects and peripheral sympathetic neurotransmission functionality during acute cocaine withdrawal syndrome in adult rats.
abstract: BACKGROUND
  Acute cocaine withdrawal syndrome (ACWS) is characterized as a set of organic alterations triggered by abrupt discontinuation of chronic cocaine consumption, usually occurring at 24-40 hours after withdrawal. However, little is known about the relationship between central and peripheral sympathetic neurotransmission during ACWS.
  
  
  OBJECTIVE
  We investigated the mechanisms involved in central and peripheral sympathetic neurotransmission and how ACWS affects the sympathetic functionality. Cocaine was administered twice daily for 5 days in Wistar rats (at least 5 in each group): on the first and second day, 15 mg/kg/i.p.; third day, 20 mg/kg/i.p.; and finally in the last two days, 30 mg/kg/i.p. Subsequently, at 1, 24, 48 and 120 h after cocaine administration the following experiments were done: (i) at the central level, behavioral tests of open-field and elevated plus maze; and (ii) at the peripheral level, tests of catecholamine release, function of α2-adrenergic receptors (α2-ARs), imidazoline receptors (I(1,2)-Rs), L-type voltage-gated (Ca(v1.2)) Ca(2+) channels and α1-ARs.
  
  
  RESULTS
  During ACWS, rats showed hypolocomotion and exacerbation of anxiogenic-effects 24 h after cocaine withdrawal. Likewise, a decrease in the catecholamine release and activity of α2-ARs/I(1,2)-Rs at 24-48 h after cocaine withdrawal was observed. A decrease in Ca(v1.2) channels and α1-ARs function at 48 h after cocaine withdrawal was observed.
  
  
  CONCLUSIONS
  The relationship of central and peripheral sympathetic neurotransmission during ACWS possibly due to a failure in activation and/or inactivation of presynaptic α2-ARs/I(1,2)-Rs, may offer a potential target for attenuating ACWS.
authors.affiliation: a Department of Pharmacology , Escola Paulista de Medicina, Universidade Federal de São Paulo , Brazil.
authors.forename: Guilherme Henrique Souza
authors.initials: GH
authors.lastname: Bomfim
authors.affiliation: b Instituto Teófilo Hernando del Medicamento , Universidad Autónoma de Madrid , Madrid , Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: García García
authors.affiliation: a Department of Pharmacology , Escola Paulista de Medicina, Universidade Federal de São Paulo , Brazil.
authors.forename: Aron
authors.initials: A
authors.lastname: Jurkiewicz
authors.affiliation: a Department of Pharmacology , Escola Paulista de Medicina, Universidade Federal de São Paulo , Brazil.
authors.forename: Neide Hyppolito
authors.initials: NH
authors.lastname: Jurkiewicz
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology; D002395:Catecholamines / Q000378:metabolism; D003042:Cocaine / Q000009:adverse effects*; D054755:Imidazoline Receptors / Q000502:physiology; D008297:Male; D018782:Maze Learning; D009043:Motor Activity; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000503:physiopathology* / Q000523:psychology*; D013564:Sympathetic Nervous System / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D014649:Vas Deferens / Q000503:physiopathology
chemical_list: D020746:Calcium Channels, L-Type; D002395:Catecholamines; D054755:Imidazoline Receptors; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D003042:Cocaine
keywords: Acute cocaine withdrawal syndrome; calcium channels; central and peripheral sympathetic neurotransmission