Effects of chronic treatment with the anticonvulsant drugs baclofen, levetiracetam and topiramate on the reinforcing strength of cocaine in rhesus monkeys

Most anticonvulsants work by increasing GABA‐mediated inhibitory brain activity. This effect may render anticonvulsants effective treatments for addiction to drugs like cocaine that stimulate brain neurotransmission. These studies examined how cocaine self‐administration in rhesus monkeys is affected by chronic treatment with three clinically available anticonvulsants: the GABA‐B receptor agonist baclofen (0.0125–0.3 mg/kg/hr, iv, n=3), levetiracetam (5–75 mg/kg/day, p.o., b.i.d., n=3), which may increase GABA release by interacting with synaptic proteins and the GABA‐A receptor agonist topiramate (0.125–0.3 mg/kg/hr, iv, n=1). Food‐reinforced responding was examined each morning under a fixed‐ratio schedule of reinforcement and cocaine self‐administration was examined once per week in evening sessions under a progressive‐ratio schedule. Baclofen and topiramate decreased responding for cocaine only at doses that also persistently disrupted food‐maintained responding (i.e., no tolerance was observed) and produced other adverse effects. Levetiracetam increased the reinforcing strength of cocaine without affecting food‐reinforced responding. The data suggest that anticonvulsant drugs do not selectively decrease cocaine‐reinforced responding in a monkey model designed to incorporate clinically relevant aspects of cocaine use and medication treatment.