Intrathecal morphine slows gastrointestinal transit in rats

Intrathecal (i.th.) (by direct lumbar puncture) and intraperitoneal (i.p.) administration of morphine (30-100 [mu]g/rat) caused a dose-related inhibition of gastrointestinal transit in the rat. Pretreatment with i.th. naloxone (5 [mu]g at -5 min) reversed the effects of i.th., but not i.p., morphine. These results suggest that the spinal cord appears to be a target site for the inhibitory effects of morphine on gastrointestinal transit in the rat.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25467/1/0000005.pd

Systemic and intracerebroventricular effects of opioid peptides in withdrawn morphine-dependent rhesus monkeys

The effects of the degradation-resistant enkephalin analogs FK 33-824 and metkephamid were determined after systemic and intracerebroventricular (i.c.v.) administration in withdrawn morphine-dependent rhesus monkeys. Both peptides suppressed completely signs of 12-hr morphine deprivation, as does the prototype mu-receptor agonist morphine. The peptides were 100 and 2000 times more potent, respectively, after i.c.v. than s.c. injection. Thus, although peptidase-resistant, these compounds have restricted entrance into the central nervous system after systemic administration. The i.c.v. administration of compounds in rhesus monkeys should prove to be a valuable tool in the study of peptide ligands for opiate receptors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25411/1/0000860.pd

Differential influence of D(1) and D(2) dopamine receptors on acute opiate withdrawal in guinea-pig isolated ileum

1. The effects exerted by D(1) and D(2) dopamine agonists and antagonists on the acute opiate withdrawal induced by μ- and κ-receptor agonists were investigated in vitro. 2. Following a 4 min in vitro exposure to morphine (moderately selective μ-agonist), [D-Ala(2), Me-Phe(4), Gly-ol(5)]enkephalin (DAMGO, highly selective μ-agonist) or U-50488H (highly selective κ-agonist) the guinea-pig isolated ileum exhibited a strong contracture after the addition of naloxone. 3. The non-selective dopamine receptor antagonist haloperidol when added before or after the opioid agonists, was able dose-dependently to prevent or to reverse the naloxone-induced contracture after exposure to μ- (morphine and DAMGO) and κ- (U-50488H) opioid agonists. The non-selective dopamine receptor agonist, apomorphine, was able to exert the same effects only at the highest concentration used. 4. The selective D(2) dopamine receptor antagonist, sulpiride, was also able to reduce dose-dependently both μ- and κ-opioid withdrawal, whereas the D(1)-receptor selective antagonist SCH 23390 did not affect either μ- or κ-opioid withdrawal. 5. Bromocriptine, a D(2) selective dopamine receptor agonist was able to increase significantly, and in a concentration-dependent manner, the naloxone-induced contracture by μ- and κ-opioid agonists, whereas SKF 38393, a D(1) selective dopamine receptor agonist, increased only the withdrawal after morphine or U50-488H. 6. Our data indicate that both D(1) and D(2) dopamine agonists and antagonists are able to influence opiate withdrawal in vitro, suggesting an important functional interaction between the dopaminergic system and opioid withdrawal at both the μ- and κ-receptor level. 7. Furthermore, the ability of sulpiride to block strongly opiate withdrawal when compared to SCH 23390, as well as the effect of bromocriptine to increase opiate withdrawal suggest that D(2) dopamine receptors may be primarily involved in the control of opiate withdrawal

Effects of U-50,488H withdrawal on catecholaminergic neurones of the rat ventricle

1. In the present study the changes in noradrenaline (NA) and dopamine (DA) content and turnover during naloxone-induced withdrawal were analysed in the right ventricle of rats chronically treated with the κ-agonist U-50,488H. 2. Rats were rendered tolerant by administration of U-50,488H twice a day for 4 days. On the day of death the animals were injected with saline or naloxone (3 mg kg(−1), s.c.) to precipitate a withdrawal syndrome. 3. After naloxone administration to U-50,488H- treated rats we found neither behaviour signs of physical dependence nor changes in the tissue content of noradrenaline (NA). However, naloxone induced a decrease in both cardiac normetanephrine (NM) levels and NA turnover. 4. Similarly, naloxone enhanced the dopamine content and decreased the 3,4-dihydroxyphenylacetic acid (DOPAC) concentration and dopamine turnover. 5. Importantly and in contrast to μ-agonists, the present results demonstrate that U-50,488H withdrawal produced a decrease in the NA and dopamine turnover, without behavioural signs of physical dependence