Acute cocaine toxicity: The effect of agents in non-seizure-induced death

Chui Chung Tseng, Robert W. Derlet, Timothy E Albertson

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Death from cocaine intoxication results from one or more of the multiple mechanisms including seizures, cardiovascular collapse, or apnea. In the free-moving rat model, continuous seizures are a major cause of death. To study other mechanisms of death unrelated to seizures in this model, we suppressed lethal seizures with diazepam (DZP) and investigated the effect of several pharmacological agents. Rats were pretreated with vehicle alone, diazepam 5 mg/kg alone, or a combination of DZP plus either nifedipine (NIFD) 2 mg/kg, propranolol (PROP) 10 mg/kg, or prazosin (PRAZ) 5 mg/kg. Five minutes after pretreatment, all animals received cocaine 100 mg/kg. Each test group consisted of 15 animals and all agents were given IP. Two animals in each group had cortical electrodes implanted. Animals that received vehicle followed by cocaine had 100% incidence of seizures and death. Those rats that received DZP alone followed by cocaine had no seizures and 53% death. Rats that received DZP plus NIFD or DZP plus PROP had suppression of seizures but no significant change in the incidence of death. The group that received DZP and PRAZ followed by cocaine had no seizures and 13% incidence of death (p< 0.001). Electroencephalogram recordings showed cortical electrical spike activity or spike-and-wave afterdischarges in all animals clinically observed to have seizures. In the absence of clinical seizure activity, no significant cortical spike activity was noted. It is concluded that animals protected from seizures with diazepam can still have nonseizure deaths after high-dose cocaine. The incidence of death in these animals is not reduced with nifedipine or propranolol pretreatment but is reduced with prazosin pretreatment.

Original languageEnglish (US)
Pages (from-to)61-65
Number of pages5
JournalPharmacology, Biochemistry and Behavior
Volume46
Issue number1
DOIs
StatePublished - 1993

Fingerprint

Diazepam
Cocaine
Toxicity
Seizures
Animals
Rats
Prazosin
Nifedipine
Propranolol
Incidence
Absence Epilepsy
Electroencephalography
Implanted Electrodes
Apnea
Cause of Death
Electrodes
Pharmacology

Keywords

  • Cocaine
  • Death
  • Diazepam
  • Prazosin
  • Respiratory arrest
  • Seizures

ASJC Scopus subject areas

  • Biochemistry
  • Behavioral Neuroscience
  • Pharmacology

Cite this

Acute cocaine toxicity : The effect of agents in non-seizure-induced death. / Tseng, Chui Chung; Derlet, Robert W.; Albertson, Timothy E.

In: Pharmacology, Biochemistry and Behavior, Vol. 46, No. 1, 1993, p. 61-65.

Research output: Contribution to journalArticle

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abstract = "Death from cocaine intoxication results from one or more of the multiple mechanisms including seizures, cardiovascular collapse, or apnea. In the free-moving rat model, continuous seizures are a major cause of death. To study other mechanisms of death unrelated to seizures in this model, we suppressed lethal seizures with diazepam (DZP) and investigated the effect of several pharmacological agents. Rats were pretreated with vehicle alone, diazepam 5 mg/kg alone, or a combination of DZP plus either nifedipine (NIFD) 2 mg/kg, propranolol (PROP) 10 mg/kg, or prazosin (PRAZ) 5 mg/kg. Five minutes after pretreatment, all animals received cocaine 100 mg/kg. Each test group consisted of 15 animals and all agents were given IP. Two animals in each group had cortical electrodes implanted. Animals that received vehicle followed by cocaine had 100{\%} incidence of seizures and death. Those rats that received DZP alone followed by cocaine had no seizures and 53{\%} death. Rats that received DZP plus NIFD or DZP plus PROP had suppression of seizures but no significant change in the incidence of death. The group that received DZP and PRAZ followed by cocaine had no seizures and 13{\%} incidence of death (p< 0.001). Electroencephalogram recordings showed cortical electrical spike activity or spike-and-wave afterdischarges in all animals clinically observed to have seizures. In the absence of clinical seizure activity, no significant cortical spike activity was noted. It is concluded that animals protected from seizures with diazepam can still have nonseizure deaths after high-dose cocaine. The incidence of death in these animals is not reduced with nifedipine or propranolol pretreatment but is reduced with prazosin pretreatment.",
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