Antagonism of the anti-conflict effects of phenobarbital, but not diazepam, by the A-1 adenosine agonist l-PIA.

The present study examined the effects of the anxiolytics diazepam and phenobarbital, the A-1 adenosine agonist N6-R-phenylisopropyladenosine (l-PIA), and the A-2 adenosine agonist 5'-N-ethylcarboxamidoadenosine (NECA) on conflict behavior. Water-restricted rats were trained to drink from a tube that was electrified (0.5 mA intensity) on a FI-29s schedule, electrification being signaled by a tone. After 3 weeks of daily 10-min sessions, the animals accepted a stable number of shocks (punished responding) and consumed a consistent volume of water (unpunished responding) per session. Different doses of l-PIA and NECA were then tested separately at weekly intervals. In addition, the effects of diazepam and phenobarbital were determined in animals pretreated with saline, l-PIA, or NECA. Neither l-PIA (15-250 nmole/kg) nor NECA (2.5-20 nmole/kg) produced a significant anti-conflict effect when administered alone. Diazepam (1.25-10 mg/kg) or phenobarbital (10-40 mg/kg) administration to saline-pretreated rats resulted in a dose-dependent increase in punished responding (shocks received) with minimal effects on unpunished responding (water intake). Neither l-PIA nor NECA pretreatment reliably altered the effects of diazepam on conflict behavior. Pretreatment with l-PIA, but not NECA, significantly reduced the anti-conflict effects of phenobarbital on conflict behavior. These data suggest that phenobarbital, but not diazepam, anti-conflict responses may involve interactions with A-1 adenosine receptors.