Antidepressant drugs appear to enhance cocaine-induced toxicity.
It has been shown that cocaine-induced convulsions and lethality appear to be mediated by serotonin and dopamine neurotransmission, respectively. However, many antidepressants considered for treatment of cocaine addiction target these monoamine systems and may thus amplify these toxic effects during relapse. In this study, the authors assessed whether pretreatment with antidepressants influences cocaine-induced toxicity in mice as well as the potency of these medications at cocaine-binding sites previously shown to be associated with cocaine toxicity. Overall, selective serotonin reuptake inhibitors (SSRIs) facilitated cocaine-induced convulsions but not lethality. Dopamine uptake inhibition facilitated cocaine-induced lethality, but not convulsion. The SSRI sertraline enhanced neither convulsions nor lethality and may be unique due to its high affinity for sigma receptors. These results have important implications for safe and effective addiction treatments.
O'Dell
L E
LE
Amethyst Technologies, Inc. Scottsdale, Arizona 85257-3773, USA.
George
F R
FR
Ritz
M C
MC
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism; D003042:Cocaine / Q000633:toxicity*; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins; D011955:Receptors, Drug / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D050486:Serotonin Plasma Membrane Transport Proteins
D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011955:Receptors, Drug; D011976:Receptors, Muscarinic; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D003042:Cocaine