Publication | Closed Access
Opposite effects of mu and kappa opiate agonists on dopamine release in the nucleus accumbens and in the dorsal caudate of freely moving rats.
921
Citations
0
References
1988
Year
The study used in vivo microdialysis and HPLC‑electrochemical detection to measure dopamine and its metabolites in the nucleus accumbens and dorsal caudate of freely moving rats, while videotaping behavior and testing the effects of mu and kappa agonists and low‑dose naloxone or beta‑funaltrexamine pretreatment. Mu agonists increased dopamine release and metabolism at lower doses in the accumbens than in the caudate, with maximal stimulation below 100% except for high‑dose methadone (>300% possibly due to hypoxia), and these effects correlated with behavioral stimulation at low doses and a biphasic inhibitory‑stimulatory pattern at higher doses; low‑dose naloxone or beta‑funaltrexamine raised the ED50 for dopamine release, whereas kappa agonists decreased dopamine release and motor activity, effects only reversed by high naloxone doses and unaffected by beta‑funaltrexamine. The abstract was truncated at 250 words.
We studied the effect of opiates acting preferentially on mu receptors, like morphine, methadone and fentanyl (mu agonists) and on kappa receptors, like U50,488, bremazocine and tifluadom (kappa agonists) on the release of dopamine (DA) and of its metabolites, dihydroxyphenylacetic acid and homovanillic acid, from the nucleus accumbens and from the dorsal caudate of freely moving rats using brain dialysis coupled to high-performance liquid chromatography with electrochemical detection. Spontaneous behavior was videotaped and analyzed by estimating the percentage of time spent by the animals in performing certain specific behavioral items. Mu agonists stimulated DA-release and metabolism in the accumbens at lower doses than in the caudate. Maximal stimulation of DA release did not exceed 100% except after high doses of methadone (10 mg/kg) which stimulated DA release in the accumbens by more than 300%, possibly as a result of hypoxia. Stimulation of DA release was associated to stimulation of behavior at low doses and to a biphasic inhibitory-stimulatory syndrome after higher doses of the opiates. Pretreatment with low doses of naloxone (0.1 mg/kg s.c.) or with the irreversible mu antagonist beta-funaltrexamine (10 nmol i.c.v.) increased the ED50 for the stimulation of DA release by the three opiates. In contrast with mu agonists, agonists of kappa receptors like U50,488, bremazocine and tifluadom decreased DA release in the accumbens and in the caudate and reduced motor activity. These effects were antagonized only by rather high doses of naloxone (2.5 mg/kg s.c.) and were not affected by pretreatment with beta-funaltrexamine (10 nmol i.c.v. (ABSTRACT TRUNCATED AT 250 WORDS)