Pharmacological manipulation of gamma-aminobutyric acid (GABA) in morphine analgesia, tolerance and physical dependence

Ing K. Ho, Horace H. Loh, E. Leong Way

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88 Scopus citations

Abstract

The findings from our laboratory indicated that pharmacological manipulations of GABA system modified morphine analgesia, tolerance and physical dependence. Elevating brain levels of GABA by slowing its destruction with aminooxyacetic acid not only antagonized the analgesic action of morphine in both non-tolerant and tolerant mice, but also enhanced the development of tolerance and physical dependence. On the other hand, blockade of postsynaptic sites of GABA receptors by bicuculline resulted in an inhibition of tolerance and dependence development. Administration of 2,4-diaminobutyric acid, an inhibitor of GABA uptake in the neurons, antagonized morphine analgesia in both non-tolerant and tolerant mice. However, it did not modify naloxone precipitated withdrawal jumping. On the contrary, β-alanine, an inhibitor of the GABA uptake process in glial cells, potentiated naloxone precipitated withdrawal jumping in morphine dependent mice, but it had no effect on morphine antinociception in both non-tolerant and tolerant mice.

Original languageEnglish (US)
Pages (from-to)1111-1123
Number of pages13
JournalLife Sciences
Volume18
Issue number10
DOIs
StatePublished - May 15 1976

Bibliographical note

Funding Information:
These studies were supported by NIDA Grant DA-01310 . I . K . Ho is a recipient of a Faculty Development Award in Pharmacology from the Pharmaceutical Manufacturers' Association Foundation .

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