Behavioral interaction of adenosine and trifluoperazine in mice

Mice were implanted with chronic indwelling cannulae in the lateral cerebral ventricle. A dose-response curve was established for the effect of i.p. injections of trifluoperazine (TFP) on spontaneous locomotor activity. In addition, the behavioral interaction of i.p. injections of TFP with intracerebroventricular (i.c.v.) injections of adenosine (ADO) was examined. TFP depressed locomotor activity in a dose-dependent manner. A dose of ADO, which had no effect on locomotor activity when given alone, enhanced the depressant effects of TFP at all doses. As a control for the specificity of this behavioral interaction, mice also were given i.p. injections of TFP in combination with i.c.v. injections of 5'-N-ethylcarboxamidoadenosine (NECA), an uptake-resistant adenosine analogue. TFP and NECA did not interact to produce a significantly more pronounced locomotor depression. These results substantiate the notion that the sedative actions of TFP involve the inhibition of adenosine uptake and thus potentiation of extracellular adenosine levels.