Systemic and intracerebroventricular administration of sodium barbital induced a place preference in rats

We have shown previously that 15 mg/kg pentobarbital induces a conditioned place preference (CPP), but it is unsuitable for intracranial administration. Since the long-acting barbiturate, sodium barbital, is soluble at a neutral pH, we tested whether it would induce a CPP when administered centrally. Furthermore, because barbital has a long duration of action, and because we obtained a significant CPP to systemically administered barbital using 30-minute conditioning trials, we tested whether longer conditioning trials would produce a more robust CPP. Using a three-compartment apparatus and an unbiased procedure, we found that systemic administration of barbital induced a significant CPP at 8 and 24 mg/kg, but not 2.7 or 72 mg/kg (i.p.). When rats were conditioned to 24 mg/kg barbital for conditioning trials of (1/2), 1, 3, or 6 hours, only the 30-min conditioning trial produced a CPP. Finally, 240 and 480 microg intracerebroventricular (ICV) barbital induced a significant CPP, but 60 or 120 microg did not. These findings suggest that: (1) like pentobarbital, barbital has reinforcing properties measured in the CPP test; (2) the CPP is impaired, rather than enhanced, by increasing the duration of drug-context pairing; and (3) the reinforcing effects of barbiturates are centrally mediated.