Potentiation of intrathecal DAMGO antinociception, but not gastrointestinal transit inhibition, by 5-hydroxytryptamine and norepinephrine uptake blockade

Abstract

Spinally administered μ opioid agonists produce potent antinociception and inhibition of gastrointesdtinal transit. Blockade of 5-hydroxytryptamine (5-HT) or norepinephrine (NE) uptake potentiates intrathecal (i.t.) DAMGO antinociception. To determine whether 5-HT and NE uptake blockade will also potentiate the gastrointestinal inhibition, mice were treated with zimelidine, desipramine or saline, followed by i.t. DAMGO and tested for tail-flick antinociception or inhibition of gastrointestinal transit. DAMGO produceed antinociception dose-dependently (ED 50 = 4.6 ng). Zimelidine (10 mg/kg, s.c., 1 hr before DAMGO) produced a 6.2-fold ng). Desipramine produced a 5.3-fold shift (ED 50 = 1.4 ng). DAMGO also produced a dose-dependent inhibition of gastrointestinal transit (ED 50 = 117 ng). However, zimelidine or desipramine treatment did not affect DAMGO inhibition of gastrointestinal transit (ED 50 = 80 ng.).