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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Baclofen, Cocaine, Dopamine Uptake Inhibitors, GABA-A Receptor Agonists, GABA-A Receptor Antagonists, GABA-B Receptor Agonists, GABA-B Receptor Antagonists, Kindling, Neurologic, Male, Mice, Piperazines, Receptors, GABA-A, Receptors, GABA-B, Seizures.
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Does pharmacological modulation of GABA ( B ) receptors affect cocaine-induced seizures in mice? Context: Previous data have demonstrated that the convulsant effects of cocaine can be modulated by compounds that increase levels of endogenous gamma-aminobutyric acid (GABA) or that directly stimulate GABA(A) receptors. To determine whether the convulsant effects of cocaine can be modulated by ligands selective for GABA(B) receptors in mice. Effects of the GABA(B) receptor agonist ((+/-)-baclofen), antagonist (phaclofen), and their combination were tested against clonic seizures induced by cocaine (75 mg/kg). Enantiomers of baclofen were used to confirm stereospecificity of (+/-)-baclofen's effects. Pharmacological specificity of (+/-)-baclofen's effects was tested by comparison against seizures induced by GBR 12909 (monoamine transporter inhibitor), pentylenetetrazole (GABA(A) antagonist), N-methyl-D-aspartate (NMDA agonist), and aminophylline (A1/A2 adenosine antagonist). Additionally, effects of (+/-)-baclofen on kindled seizures induced by repeated administration of cocaine (60 mg/kg every 24 h for 6 days) were evaluated. The inverted screen test was used to assess behavioral side effects of baclofen. (+/-)-Baclofen dose-dependently inhibited acute (ED50=4.1 mg/kg) and kindled (6.4 mg/kg) seizures induced by cocaine at doses somewhat lower than those producing behavioral side effects (11.5 mg/kg), and these effects were stereospecific. (+/-)-Baclofen suppressed seizures induced by GBR 12909 but not by pentylenetetrazole, NMDA, and aminophylline, suggesting selectivity of its anticonvulsant effects for monoamine-related mechanisms. Finally, phaclofen dose-dependently enhanced the convulsant effects of a threshold dose of cocaine (60 mg/kg).
assistant
Modulation of GABA(B) receptors can affect seizures induced by cocaine. This molecular mechanism may be involved in seizures induced by cocaine or, alternatively, may function as an independent inhibitory mechanism against seizures arising from blockade of monoamine uptake. Final Decision: yes