Journal article
Progesterone withdrawal: II: insensitivity to the sedative effects of a benzodiazepine
Brain research, v 807(1), pp 91-100
1998
PMID: 9757006
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Previous results from this lab have demonstrated that the GABA-modulatory steroid 3α-OH-5α-pregnan-20-one (3α,5α-THP) exhibits withdrawal properties, increasing anxiety [M.A. Gallo, S.S. Smith, Progesterone withdrawal decreases latency to and increases duration of electrified prod burial: a possible rat model of PMS anxiety, Pharmacol. Biochem. 46 (1993) 897–904.] and seizure susceptibility [S.S. Smith, Q.H. Gong, F.-C. Hsu, R.S. Markowitz, J.M.H. ffrench-Mullen, X. Li, GABA
A receptor α4 subunit suppression prevents withdrawal properties of an endogenous steroid, Nature 392 (1998) 926–930.] upon abrupt discontinuation after chronic administration of its parent compound, progesterone (P), in a manner similar to other GABA-modulatory drugs. Further, we have demonstrated that withdrawal from P produces insensitivity to the potentiating effects of the benzodiazepine (BDZ) lorazepam (LZM) on GABA-gated Cl
− current [A.-M.N. Costa, K.T. Spence, S.S. Smith, J.M.H. ffrench-Mullen, Withdrawal from the endogenous steroid progesterone results in GABA
A currents insensitive to BDZ modulation in rats CA1 hippocampus, J. Neurophysiology 74 (1995) 464–469; S.S. Smith, Q.H. Gong, F.-C. Hsu, R.S. Markowitz, J.M.H. ffrench-Mullen, X. Li, GABA
A receptor α4 subunit suppression prevents withdrawal properties of an endogenous steroid, Nature 392 (1998) 926–930.], assessed using whole cell patch clamp procedures on pyramidal neurons acutely dissociated from CA1 hippocampus. The purpose of the present study was to examine the withdrawal effects of P on the sedative potency of LZM, tested behaviorally as the ability to maintain position on a variable speed treadmill following LZM administration (0.75 mg/kg). Both continuous (continuous release P capsule, single withdrawal) as well as discontinuous (multiple P injection, multiple withdrawal) paradigms were tested. Longer continuous release paradigms were more effective in abolishing the sedative effects of LZM, without producing a change in baseline response. The LZM insensitivity observed following the multiple withdrawal paradigm was prevented by prior intraventricular administration of antisense oligonucleotide against the α4 subunit of the GABA
A receptor. These results support the hypothesis that withdrawal from P decreases the behavioral response to LZM as a direct result of increases in the α4 subunit of the GABA
A receptor. Withdrawal from P occurs endogenously during pre-menstrual and post-partum periods, when decreased response to BDZ has been reported.
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Details
- Title
- Progesterone withdrawal: II: insensitivity to the sedative effects of a benzodiazepine
- Creators
- Maria H Moran - Allegheny University of the Health SciencesMichelle Goldberg - Allegheny University of the Health SciencesSheryl S Smith - Allegheny University of the Health SciencesSusan S Smith - [Retired Faculty]
- Publication Details
- Brain research, v 807(1), pp 91-100
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- [Retired Faculty]
- Web of Science ID
- WOS:000076367800011
- Scopus ID
- 2-s2.0-0032487670
- Other Identifier
- 991019167537704721
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