Rats were allowed to self-administer cocaine on a fixed daily ratio over a period of 3 weeks (learning to push a button to receive cocaine). After one week of withdrawal, the effect of SCH-442416 on adenosine receptor modulation was tested against reinstatement to cocaine seeking induced by cues, cocaine, and the dopamine D2 receptor agonist, quinpirole. SCH-442416 was dissolved in dissolved in 33% DMSO and 66% ddH20 and administered by intraperitoneal injection as a dose of 0.3 mg/kg, 1 mg/kg, and 3 mg/kg and administered prior to each extinction training session. Administration of SCH 442416 had no direct effects on the extinction of learned behavior but did produce a dose-dependent persistent impairment of cocaine- and quinpirole-induced seeking.

Rat retinal Müller cells were treated with 0.1, 1, 10 uM SCH-442416 for 24 hours at hydrostatic pressures of 0, 20, 40, 60, 80 mmHg. Expression of glutamine synthetase (GS) and glutamate aspartate transporter (GLAST) was monitored using real-time PCR and Western Blotting. A significant increase in expression of GS and GLAST was observed at 40 mmHg pressure and expression was further enhanced by treatment with 10 uM SCH-442416 at 40 mmHg pressure.