Relationship between central behavioral effects and peripheral sympathetic neurotransmission functionality during acute cocaine withdrawal syndrome in adult rats

• Published in: The American journal of drug and alcohol abuse Vol. 42; no. 1; pp. 63 - 76
• Main Authors: Bomfim, Guilherme Henrique Souza, García, Antonio García, Jurkiewicz, Aron, Jurkiewicz, Neide Hyppolito
• Format: Journal Article
• Language: English
• Published: England Informa Healthcare 02-01-2016; Taylor & Francis Ltd
• Subjects: Acute cocaine withdrawal syndrome; Animals; Behavior; calcium channels; Calcium Channels, L-Type - physiology; Catecholamines - metabolism; central and peripheral sympathetic neurotransmission; Cocaine; Cocaine - adverse effects; Drug use; Effects; Imidazoline Receptors - physiology; Male; Maze Learning; Motor Activity; Neurotransmitters; Rats; Receptors, Adrenergic, alpha-1 - physiology; Receptors, Adrenergic, alpha-2 - physiology; Rodents; Substance Withdrawal Syndrome - metabolism; Substance Withdrawal Syndrome - physiopathology; Substance Withdrawal Syndrome - psychology; Sympathetic Nervous System - physiology; Synaptic Transmission - physiology; Vas Deferens - physiopathology; Acute cocaine withdrawal syndrome; calcium channels; central and peripheral sympathetic neurotransmission
• ISSN: 0095-2990; 1097-9891
• DOI: 10.3109/00952990.2015.1094082

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 α
2
-adrenergic receptors (α
2
-ARs), imidazoline receptors (I
1,2
-Rs), L-type voltage-gated (Ca
v1.2
) Ca
2+
channels and α
1
-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 α
2
-ARs/I
1,2
-Rs at 24-48 h after cocaine withdrawal was observed. A decrease in Ca
v1.2
channels and α
1
-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 α
2
-ARs/I
1,2
-Rs, may offer a potential target for attenuating ACWS.