Place preference and microdialysis studies with two derivatives of methylphenidate.

Conditioned place preference studies with derivatives of dl-threo-methylphenidate (Ritalin) which bear a bromine atom or a methoxy group on the para position of the phenyl ring are reported. Both derivatives, as well as methylphenidate itself, induced a significant increase in place preference when administered i/p to rats at 10 mg/Kg, compared with saline conditioned controls. The change for p-bromomethylphenidate was slightly greater than that seen for methylphenidate or p-methoxymethylphenidate. Extracellular dopamine in the striatum, and locomotor activity, were also increased by i/p administration of p-methoxymethylphenidate (20 mg/Kg) to a similar extent to the increases seen with this dose of methylphenidate or p-bromomethylphenidate in an earlier study (Pan et al. Eur. J. Pharmacol. 264: 177-182, 1994). Administration of p-methoxymethylphenidate failed to abolish increases in extracellular dopamine and locomotor activity induced by subsequent administration of cocaine (20 mg/Kg). It is concluded that the methylphenidate derivatives share the general pharmacological properties of other psychostimulant drugs.