European Journal of Pharmacology, 68 (1980) 33--40 33 © Elsevier/North-Holland Biomedical Press A COMPARISON OF THE EFFECTS OF METHYLPHENIDATE AND AMPHETAMINE ON THE SIMULTANEOUS RELEASE OF RADIOLABELLED DOPAMINE AND p- OR m-TYRAMINE FROM RAT STRIATAL SLICES LILLIAN E. DYCK, ALAN A. BOULTON and ROLAND S.G. JONES Psychiatric Research Division, University Hospital, Saskatoon, Saskatchewan, Canada S7N OXO Received 7 November 1979, revised MS received 6 February 1980, accepted 18 August 1980 L.E. DYCK, A.A. BOULTON and R.S.G. JONES, A comparison of the effects of methylphenidate and amphet- amine on the simultaneous release of radiolabeiled dopamine and p- or m-tyramine from rat striatal slices, Euro- pean J. Pharmacol. 68 (1980) 33--40. The release of [ 14C]dopamine (DA) from slices of rat caudate nucleus was studied simultaneously with the release of either [3HlPara-tyramine (pTA) or [3H]meta-tyramine (mTA). Amphetamine (10 -s M)caused a large concurrent release of [ 14C ]DA and. [3H ]pTA; similar results were obtained when [ 14C ]DA and [3H ]raTA release were studied. The release of all three amines by amphetamine was quantitatively similar. In contrast, methyl- phenidate caused a release of [3H]pTA similar to that seen with amphetamine, but only a very small simultaneous release of [14C]DA. [3H]mTA was also strongly released by methylphenidate concurrent with a minimal release of [ 14C ]DA. The inclusion of reserpine in the incubation medium had no detectable effect on the release of any of the three amines by amphetamine. Methylphenidate-induced release of tritiated mTA and pTA was also un- affected by reserpine. However, the release of [14C]DA by methylphenidate was potentiated in the presence of reserpine. The uptake of radiolabelled pTA, mTA and DA was inhibited by both amphetamine and methyl- phenidate, although amphetamine was a stronger inhibitor of the uptake of all three amines. It is suggested that release of endogenous tyramines may be involved in mediating some actions of psychomotor stimulant drugs. Amphetamine Dopamine release Methylphenidate m-Tyramine release p-Tyramine release 1. Introduction Amphetamine and methylphenidate both increase locomotor activity and produce stereotyped behaviour in rodents (Scheel- Kriiger, 1971). It is widely believed that these actions result from release of brain catechol- amines, primarily dopamine (DA), (Scheel- Krtiger, 1971; Thornburg and Moore, 1973; Creese and Iversen, 1975). However, the mechanism of this release appears to be dif- ferent for the two drugs. The actions of amphetamine are blocked by prior administra- tion of a-methyl-p-tyrosine but not by reser- pine, whilst the reverse is true for methyl- phenidate (Weissman et al., 1966; Scheel- Kriiger, 1971). These observations are cur- rently believed to demonstrate that amphet- amine releases newly synthesized DA (pre- sumably from an extravesicular storage site), whereas methylphenidate releases the amine from storage vesicles (Thornburg and Moore, 1973; Chieuh and Moore, 1975). However, other evidence, which confirms that amphet~ amine releases extravesicular DA, indicates that methylphenidate also acts at sites in the cell membrane (Ross, 1977a; Braestrup, 1977). Both the stereotypy and locomotor stimula- tion induced by amphetamine in rats have been suggested to result from release of dopa- mine in the striatum (Creese and Iversen, 1975). Previous reports have demonstrated the existence of relatively high concentrations, high affinity uptake and depolarization- induced release of the trace amines, meta-