Behavioural Brain Research 115 (2000) 55–64
Research report
Anti-sense oligonucleotides, for progestin receptors in the VMH
and glutamic acid decarboxylase in the VTA, attenuate
progesterone-induced lordosis in hamsters and rats
Cheryl A. Frye*, Rebecca E. Murphy, Steven M. Platek
Department of Psychology, The Uni6ersity at Albany – SUNY,
1400
Washington A6enue, Albany, NY
12222
, USA
Received 14 October 1999; received in revised form 26 April 2000; accepted 2 May 2000
Abstract
Immunocytochemical (ICC) staining for progesterone (P) receptors (PRs) and glutamic acid decarboxylase (GAD), the enzyme
responsible for GABA production, reveal that there are many PRs in the ventral medial hypothalamus (VMH) and many GAD
containing neurons in the ventral tegmental area (VTA). To investigate P’s action on lordosis in the VMH and VTA, anti-sense
oligos specific to PRs and GAD
65&67
were intracerebrally infused into the VMH and VTA of 24 ovariectomized hamsters and 40
ovariectomized rats. Estradiol benzoate (2 mg) primed hamsters and rats were infused to the VMH and the VTA with either PR
(250 ng/1.0 ml infusion) or GAD (500 ng/1.0 ml infusion) anti-sense oligos, their scramble controls, or saline vehicle at hour 0 and
again at hour 24. At hr 44, rodents were subcutaneously injected with P (500 mg) and were tested for sexual receptivity with a male
4 h later. There were significant reductions in lordosis of hamsters and rats following PR anti-sense infusions to the VMH
compared to scrambled or vehicle control infusions. Effects of PR anti-sense to the VMH were not different from combined VMH
and VTA PR anti-sense infusions; however, VMH infusions reduced lordosis compared to VTA-only anti-sense infusions. GAD
anti-sense infusions reduced lordosis when infused into the VTA, compared to scrambled or saline vehicle infusions. Lordosis
responsiveness following VTA GAD anti-sense infusions was not different from combined VMH and VTA infusions, but VTA
infusions of GAD anti-sense reduced lordosis compared to VMH-only anti-sense infusions. These data suggest that in the VMH,
PRs are important for P-facilitated lordosis, whereas in the VTA, GABAergic neurons may be an important substrate for
mediating P’s actions on lordosis of rodents. © 2000 Elsevier Science B.V. All rights reserved.
Keywords
:
Neurosteroid; Extra-genomic; GABA; Receptivity; Ventromedial hypothalamus; Ventral tegmental area
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1. Introduction
Estrous cycle variations in estradiol (E
2
) and proges-
terone (P) result in ovulation and receptivity in rodents.
Receptivity is characterized by females’ display of lor-
dosis in response to appropriate environmental stimula-
tion, which receptive females typically seek out from
males. Because receptive behavior can be readily con-
trolled, induced, observed, and quantified in ovariec-
tomized (ovx) rodents by systemic administration of E
2
and P [7], receptivity is an ideal behavioral assay for
investigating hormone action in the brain.
An important brain site involved in receptivity is the
ventral medial hypothalamus (VMH): when E
2
and P
are applied to the VMH of ovx rats [43,46,47], lordosis
is readily elicited. Receptivity in ovx, E
2
-primed ham-
sters requires P to both the VMH and the ventral
tegmental area (VTA) [5,44]. Because of their extreme
reliance on P, hamsters have been utilized extensively to
examine the mechanisms of P’s actions in the VTA.
Studies utilizing P conjugated to the macromolecule
bovine serum albumin (P:BSA), which cannot permeate
cell membranes [45], reveal that P:BSA quickly induces
lordosis when applied to the VTA following free P to
* Corresponding author. Tel.: +1-518-4424836; fax: + 1-518-
4424867.
E-mail address
:
cafrye@cnsunix.albany.edu (C.A. Frye).
0166-4328/00/$ - see front matter © 2000 Elsevier Science B.V. All rights reserved.
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