[Regulation of the central opioidergic nervous system on the emotional state of anxiety and its possible mechanisms].
The spontaneous withdrawal from morphine in morphine-dependent rats significantly decreased the duration of active interaction in social interaction test and the number of licks during the shock-punished period in Vogel's conflict procedure, which were attenuated by buspirone, a 5-HT1A agonist, as well as para-chlorophenylalanine (PCPA), an inhibitor of tryptophan hydroxylase. Naltrexone (NTX), a potent opioid receptor antagonist, also dose- and time-dependently reduced both indices mentioned above, which was blocked by morphine or PCPA and was enhanced by 5-hydroxytryptophan, a precursor of 5-HT. In the test of neurotransmitter releases in rat brain slices, both morphine-withdrawal and NTX enhanced high potassium(30mM)-induced 5-HT release in slices of the area of the raphe nucleus. These results suggested that both morphine-withdrawal and NTX produced anxieties in morphine-dependent and normal rats, respectively, which were mediated by the central 5-HTergic neurotransmission. Central opioidergic neurons inhibited 5-HTergic neurons tonically and presynaptically. Such an effect was reduced or blocked by NTX, or during morphine-withdrawal, and 5-HTergic neurons were disinhibited, leading to a state of anxiety.
Zhang
H T
HT
Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing.
D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D009020:Morphine / Q000009:adverse effects*; D009021:Morphine Dependence / Q000378:metabolism*; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D009292:Narcotic Antagonists; D012701:Serotonin; D009271:Naltrexone; D009020:Morphine