The spinal cord as a site of opioid effects on gastrointestinal transit in the mouse

Intrathecal (i.t.) administration of morphine (1, 3 or 10 micrograms) effectively inhibited the passage of a radiolabeled marker through the gastrointestinal tract of mice. This effect was reversed by pretreatment with naloxone (2 mg/kg s.c.). Transection of the spinal cord at the level of the second thoracic vertebra (T2) slowed control transit when measured after 4 hr; nevertheless, i.t. morphine inhibited transit in these paralyzed animals. Similarly, i.c.v. administration of morphine (1, 3 or 10 micrograms) inhibited transit regardless of whether the spinal cord was transected at T2. Lower efficacy was seen with i.p. (10-300 micrograms/kg) or i.v. (10 micrograms) morphine than with comparable doses given i.t. (10 micrograms). Intrathecal administration (1, 3 or 10 micrograms) of the proposed selective delta opioid agonist peptides, D-Ala2-D-Leu5-enkephalin, D-Pen2-L-Cys5-enkephalin or i.t. administration of D-Ser2-Leu-enkephalin-(Thr6) (10 micrograms) were effective in inhibiting gastrointestinal transit. In contrast, the proposed kappa agonists, ketocyclazocine (1, 3 or 10 micrograms) or dynorphin-(1-13) (1, 10 or 100 micrograms), did not affect transit after i.t. administration. Dynorphin-(1-13) (10, 30 or 100 micrograms) or dynorphin-(1-9) (10, 30 or 100 micrograms) similarly did not affect transit after i.c.v. administration. Whereas D-Ala2-D-Leu5-enkephalin (1, 3 or 10 micrograms) and D-Ser2-Leu-enkephalin-(Thr6) (10 micrograms) were also efficacious in inhibiting transit by the i.c.v. route, the more delta selective D-Pen2-L-Cys5-enkephalin (1, 3, 10 or 20 micrograms) was not.(ABSTRACT TRUNCATED AT 250 WORDS)