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 and Methods: 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) Ca²⁺ 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.

KEYWORDS:

• Acute cocaine withdrawal syndrome
• central and peripheral sympathetic neurotransmission
• calcium channels

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This work was supported by “Fundação Coordenação de Aperfeiçoamento de Pessoal de Nível Superior” – CAPES (BEX 8477/13-2)‏ and “Fundação de Amparo a Pesquisa do Estado de São Paulo” – FAPESP.