Modification of quasi-morphine withdrawal with serotonin agonists and antagonists: evidence for a role of serotonin in the expression of opiate withdrawal
✍ Scribed by Mark S. Kleven; Sheldon B. Sparber
- Publisher
- Springer
- Year
- 1989
- Tongue
- English
- Weight
- 663 KB
- Volume
- 98
- Category
- Article
- ISSN
- 0033-3158
No coin nor oath required. For personal study only.
✦ Synopsis
Methylxanthines produce a quasi-morphine withdrawal syndrome (QMWS) in opiate naive rats. Additionally, methylxanthine-induced suppression of conditioned behavior in rats is reversed by the alpha2 adrenergic agonist clonidine which also attenuates true opiate withdrawal and the QMWS. Therefore, the operant behavioral effects of 3-isobutyl-l-methylxanthine (IBMX) provide a model with which to study mechanisms involved in the expression of opiate withdrawal. In order to examine the role of serotonin (5-HT) in the rate-decreasing effects of IBMX on operant behavior, the 5-HT precursor 5-hydroxytryptophan, and 5-HT reuptake blocker fluoxetine were administered in combination with IBMX to rats performing a fixed-ratio 30 operant for food reinforcement. Both drugs failed to reverse the behavioral suppression caused by relatively low doses of IBMX, suggesting that elevated 5-HT neurotransmission contributes to, rather than attenuates, the QMWS. The relatively selective 5-HT2 antagonists mianserin and pirenperone blocked the [BMX-induced suppression, whereas the classic 5-HT antagonist methysergide had no effect. The results indicate that the operant behavioral effects of IBMX and possibly the QMWS may be mediated by serotonergic mechanisms.