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

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)) 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.

Evidence for the involvement of the noradrenergic system, dopaminergic and imidazoline receptors in the antidepressant-like effect of tramadol in mice.

The involvement of the noradrenergic system, imidazoline, dopaminergic and adenosinergic receptors in the antidepressant-like action of tramadol in the mouse forced swimming test (FST) was evaluated in this study. The antidepressant-like effect of tramadol (40mg/kg, per oral, p.o.) in the FST was blocked with yohimbine (1mg/kg, i.p., an alpha(2)-adrenoceptor antagonist), alpha-methyl-para-tyrosine methyl ester (AMPT, 100mg/kg, i.p., an inhibitor of tyrosine hydroxylase), efaroxan (1mg/kg, i.p., an imidazoline I(1)/alpha(2)-adrenoceptor antagonist), idazoxan (0.06mg/kg, i.p., an imidazoline I(2)/alpha(2)-adrenoceptor antagonist), antazoline (5mg/kg, i.p., a ligand with high affinity for the I(2) receptor), haloperidol (0.2mg/kg, i.p., a non selective dopamine receptor antagonist), SCH23390 (0.05mg/kg, subcutaneously, s.c., a dopamine D(1) receptor antagonist), sulpiride (50mg/kg, i.p., a dopamine D(2) and D(3) receptor antagonist) but was not reversed by prazosin (1mg/kg, intraperitoneally, i.p., an alpha(1)-adrenoceptor antagonist) and caffeine (3mg/kg, i.p., a nonselective adenosine receptor antagonist). Monoamine oxidase-A and -B (MAO-A and MAO-B) activities were neither inhibited in the whole brain nor in specific brain regions of mice treated with tramadol. These data demonstrated that the antidepressant-like effect caused by oral administration of tramadol in the mouse FST is mediated by the noradrenergic system, dopaminergic and imidazoline receptors.