Substitution of psychoactive drugs
in pentobarbital-dependent rats

by
Yutrzenka GJ, Patrick GA, Rosenberger W.
Department of Physiology and Pharmacology,
University of South Dakota School of Medicine, Vermillion.
Drug Alcohol Depend 1990 Aug; 26(1):9-17


ABSTRACT

The substitution of either bromazepam, diazepam, methaqualone, mazindol, nortriptyline or bupropion for pentobarbital, in dependent rats, was assessed using a continuous drug infusion method. Male, Sprague-Dawley rats were made dependent on pentobarbital during 12 days of continuous, intraperitoneal, pentobarbital infusion. On Day 13, pentobarbital was replaced with either saline, vehicle, or one of the drugs of interest and rats were infused for 24 h. On Day 14, all rats were infused, for 24 h, with saline. Changes in both body weight and behavioral indices of withdrawal were assessed during Day 13 and 14. It was observed that bromazepam and methaqualone substituted for pentobarbital in a dose-dependent fashion. Diazepam also substituted in pentobarbital dependent rats but, inexplicably, the low dose of diazepam provided better substitution than did the higher dose. On the other hand, neither mazindol or nortriptyline substituted for pentobarbital and there was a tendency for exacerbation of the withdrawal signs. Finally, it was noted that the low dose of bupropion appeared to decrease the severity of the withdrawal symptoms. The data supports the view that the substitution of compounds for pentobarbital, in dependent rats, is limited to those compounds which, presumably, possess similar mechanisms of action in the CNS.
GAD
GABA
Anxiety
Bupropion
Diazepam
Buspirone
Zopliclone
Barbiturates
Nortryptiline
Methaqualone
Benzodiazepines
Amobarbital: structure
Secobarbital: structure
The sodium amytal test
Pentobarbital (Nembutal) : structure

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