Methionine-enkephalin and beta-endorphin levels in spleen and thymus gland of morphine tolerant-dependent and abstinent rats.
The effect of chronic administration of morphine and abrupt and naloxone-precipitated withdrawal on the levels of beta-endorphin and methionine-enkephalin in spleen, adrenals and thymus glands of Sprague-Dawley rats was determined. Rats were made tolerant to and dependent on morphine by subcutaneous implantation of 6 morphine pellets (75 mg morphine in each) during a 7-day period. The tolerant-dependent (with pellets intact) and abstinent (pellets removed 18 hours earlier) rats were sacrificed. In another group, rats with pellets intact were injected with naloxone and sacrificed 10 min later (precipitated abstinence). The weights of the tissues under any of the above treatments did not change nor did the levels of methionine-enkephalin and beta-endorphin in adrenals. The level of beta-endorphin was elevated in the spleen and thymus of morphine tolerant-dependent rats, while the levels of methionine-enkephalin in rats undergoing abrupt or naloxone-precipitated abstinence were significantly higher than in their respective placebo controls. The levels of methionine-enkephalin in the thymus gland of rats with placebo and morphine pellets left intact did not differ. It is concluded that in morphine tolerant-dependent rats the levels of beta-endorphin in spleen and thymus are elevated. During abrupt and naloxone-precipitated abstinence, the levels of methionine-enkephalin in the thymus gland are significantly elevated possibly due to an inhibition of their release. Since these opioid peptides have been implicated in immunomodulation, and alterations were seen in organs controlling immune function, the present results may be helpful in explaining altered immune function in morphine dependent and abstinent states.
Bhargava
H N
HN
Department of Pharmacodynamics, University of Illinois, Chicago 60612.
Ramarao
P
P
Gulati
A
A
Gudehithlu
K P
KP
Tejwani
G A
GA
D000311:Adrenal Glands / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D004361:Drug Tolerance; D004744:Enkephalin, Methionine / Q000378:metabolism*; D008297:Male; D009020:Morphine / Q000009:adverse effects; D009021:Morphine Dependence / Q000378:metabolism*; D009270:Naloxone / Q000494:pharmacology; D009929:Organ Size; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism*; D001615:beta-Endorphin / Q000378:metabolism*
D009270:Naloxone; D004744:Enkephalin, Methionine; D001615:beta-Endorphin; D009020:Morphine