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• W2096286070 abstract "O’DONNELL, J. M. AND S. FRITH. Behavioral effects of family-selective inhibitors of cyclic nucleotide phosphodiesterases. PHARMACOL BIOCHEM BEHAV 63(1) 185–192, 1999.—The effects of family selective inhibitors of phosphodiesterase (PDEl, PDE2, PDE3, PDE4, and PDE5) on the behavior of rats under either a differential-reinforcement-of-low-rate (DRL) 72-s schedule or a variable-interval (VI) 30-s schedule were determined; previous work has shown that antidepressant drugs increase reinforcement rate under long DRL schedules. The PDE4-selective inhibitor rolipram (0.03–0.1 mg/kg) reduced response rate and increased reinforcement rate under the DRL schedule in a dose-dependent manner; similar effects were observed with the tricyclic antidepressant drug desipramine (3–10 mg/kg). Both of these drugs produced biphasic effects on behavior maintained under the VI schedule, increasing response rate at the lower doses tested (rolipram: 0.003 mg/kg; desipramine: 0.03 mg/kg) and decreasing response rate at higher doses (rolipram: 0.1 mg/kg; desipramine: 0.3–18 mg/kg). Of the other PDE inhibitors tested, only the PDE5-selective inhibitor zaprinast (10 mg/kg) produced an antidepressant-like effect on DRL behavior. However, in contrast to the biphasic effects of rolipram and desipramine on VI behavior, zaprinast produced monotonic decreases in response rate (10–30 mg/kg). The PDE2-selective inhibitor trequinsin produced biphasic effects on response rate under the VI schedule, increasing rates at low doses (3–5.6 mg/kg) and decreasing rates at higher doses (18–30 mg/kg). Trequinsin also reduced response rate under the DRL schedule (30 mg/kg); however, the reduction in response rate was not accompanied by increased reinforcement rate. The PDE3-selective inhibitor milrinone (1–10 mg/kg) tended to increase response rates under both schedules while the PDE1-selective inhibitor vinpocetine did not affect behavior at the dose range tested (1–30 mg/kg). These findings suggest that inhibition of PDE4 results in a rather unique pattern of behavioral effects, most notably an antidepressant-like effect on DRL behavior. It remains to be determined if a similar effect produced by zaprinast also implicates PDE5 in the mediation of antidepressant activity or represents an effect of this drug on PDE4 activity at high doses." @default.
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• W2096286070 date "1999-05-01" @default.
• W2096286070 modified "2023-09-27" @default.
• W2096286070 title "Behavioral Effects of Family-Selective Inhibitors of Cyclic Nucleotide Phosphodiesterases" @default.
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• W2096286070 doi "https://doi.org/10.1016/s0091-3057(98)00267-6" @default.
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