Methocarbamol: evaluation of reinforcing and discriminative stimulus effects.
The behavioural effects of methocarbamol, a centrally acting muscle relaxant, were assessed using self-injection procedures in baboons and drug discrimination procedures in baboons and rats. The ability of methocarbamol to maintain self-injection was examined using a drug substitution procedure. Responding was maintained initially by cocaine delivery (0.32mg/kg/injection, i.v.). Each drug injection was followed by a 3-h timeout allowing a maximum of eight injections per day. Methocarbamol doses or vehicle were substituted for cocaine for a period of 15 or more days each, with re-establishment of responding under cocaine after each substitution. Evaluation of a wide range of methocarbamol doses (1.0-32mg/kg/injection) showed that this compound maintained rates of self-injection at vehicle control levels, which were below those maintained by cocaine. The discriminative stimulus effects of methocarbamol were studied in baboons trained to discriminate either lorazepam (1.8mg/kg, p.o.) or pentobarbital (10.0mg/kg, p.o.) from the no-drug condition and in rats trained to discriminate lorazepam (1.0mg/kg, i.p.), diazepam (1.0mg/kg, i.p.), or pentobarbital (10.0mg/kg, i.p.) from the no-drug condition using a two-lever, food-maintained drug discrimination procedure. Evaluation of a range of doses in baboons (10-180mg/kg, p.o.) and rats (32-180mg/kg, i.p.) showed that methocarbamol did not occasion drug-lever responding at any dose. Methocarbamol did not produce changes in response rates in baboons, but higher doses severely suppressed response rates in rats. The present experiments show that the behavioral profile of methocarbamol is clearly distinguishable from that of barbiturates and benzodiazepines. Taken together with analogous studies with other sedative-anxiolytic drugs, these results suggest that methocarbamol has a relatively low likelihood of abuse.
Department of Psychiatry and Behavioral Sciences The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA NIDA Addiction Research Center, Baltimore, MD.
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Sannerud
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Ator
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Griffiths