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

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Abstract

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 ofl-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. Neitherl-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). Neitherl-PIA nor NECA pretreatment reliably altered the effects of diazepam on conflict behavior. Pretreatment withl-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.

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Authors and Affiliations

  1. Department of Psychiatry, Wayne State University, 48202, Detroit, MI, USA

    Randall L. Commissaris & Harvey J. Altman

  2. Department of Physiology, School of Medicine, Wayne State University, 48202, Detroit, MI, USA

    Gracia M. Damian & Robin A. Barraco

  3. Department of Pharmaceutical Sciences, College of Pharmacy & AHP, Wayne State University, 48202, Detroit, MI, USA

    Randall L. Commissaris, Timothy C. McCloskey & Brian D. Brown

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  1. Randall L. Commissaris
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  2. Timothy C. McCloskey
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  3. Gracia M. Damian
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  4. Brian D. Brown
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  5. Robin A. Barraco
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  6. Harvey J. Altman
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Commissaris, R.L., McCloskey, T.C., Damian, G.M. et al. Antagonism of the anti-conflict effects of phenobarbital, but not diazepam, by the A-1 adenosine agonistl-PIA. Psychopharmacology 102, 283–290 (1990). https://doi.org/10.1007/BF02244091

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  • DOI: https://doi.org/10.1007/BF02244091

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