Noradrenergic mechanisms appear not to be involved in cocaine-induced seizures and lethality

In the present study we have investigated the effects of compounds which increase synaptic levels of noradrenaline on cocaine-induced seizures and lethality in mice. The noradrenaline uptake blocker desipramine (0.3, 3, 30 mg/kg i.p.; 1h pretreatment) and the alpha 2-antagonists idazoxan (0.05, 0.5, 5 mg/kg i.p.; 15 min) and RX811059A (0.01, 0.1, 1 mg/kg i.p.; 15 min) neither reduced nor increased the number of animals having convulsions in the 10 min following administration of cocaine (45, 60 mg/kg i.p.). None of these drugs increased lethality when assessed 10 minutes after 60 mg/kg cocaine and the alpha 2-antagonists did not protect against the lethal effects of a 90 mg/kg dose. On the other hand, desipramine significantly reduced the number of animals dying after this high dose of cocaine. These results suggest that noradrenergic mechanisms do not promote cocaine-induced convulsions and lethality - an important observation in light of the growing use of desipramine for initiation of abstinence in cocaine-dependent outpatients.