ro13-9904 and Amphetamine-Related-Disorders

Ceftriaxone (a beta-lactam antibiotic) has recently been identified as having the rare ability to increase the expression and functional activity of the glutamate transporter subtype 1 (GLT-1) in rat spinal cord cultures. GLT-1 has been implicated in diverse neurological disorders and in opioid dependence and withdrawal. It has been speculated that it might also be involved in the physical dependence and withdrawal of other abused drugs, but demonstration of this property can be difficult in mammalian models. Here, we demonstrate for the first time using a planarian model that ceftriaxone attenuates both the development of physical dependence and abstinence-induced withdrawal from cocaine, amphetamine, methamphetamine, and a benzodiazepine (clorazepate) in a concentration-related manner. These results suggest that physical dependence and withdrawal from several drugs involve a common - beta-lactam-sensitive - mechanism in planarians. If these findings can be shown to extend to mammals, beta-lactam antibiotics might represent a novel pharmacotherapy or adjunct approach for treating drug abuse or serve as a template for drug discovery efforts aimed at treating drug abuse, recovery from drug abuse, or ameliorating the withdrawal from chronic use of therapeutic medications.

Topics: Amphetamine; Amphetamine-Related Disorders; Animals; Anti-Bacterial Agents; Ceftriaxone; Clorazepate Dipotassium; Cocaine; Cocaine-Related Disorders; Dose-Response Relationship, Drug; Excitatory Amino Acid Transporter 2; Methamphetamine; Models, Animal; Motor Activity; Planarians; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors