[Abstract Title]. - Society for Neuroscience

Poster
273. Basal Ganglia: Transmitters and Neuromodulation I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 273.4/II19
Topic: D.15.a. Transmitters and neuromodulation
Title: Intranasal progesterone administration drives dopaminergic activity in the basolateral
amygdala and neostriatum of rats
Authors: M. A. DE SOUZA SILVA 1 , B. TOPIC 1 , J. P. HUSTON 1 , *C. MATTERN 2 ;
1 Inst. of Physiological Psychology, Univ. of Düsseldorf, Düsseldorf, Germany; 2 Mattern
Pharmaceuticals AG, Stans, Switzerland
Abstract: The female steroid hormone progesterone has several physiological actions and
regulates sexual and reproductive behaviors. It also influences memory and emotionality.
Therapeutically, progesterone has been used as a contraceptive for the treatment of menopausal
symptoms, and there is evidence that it is neuroprotective following central nervous system
injury. Since progesterone undergoes a high first-pass metabolism, the intranasal route would
seem be a more efficient alternative for delivery. In this study we examined the effects of
intranasal administration of progesterone on dopaminergic activity in the basolateral amygdala
and neostriatum. We also compared the effectiveness of intranasal vs systemic administered
progesterone. Male Wistar rats were implanted with guide cannulae aimed at basolateral
amygdala and neostriatum. Three to 5 days latter, they were anesthetized with urethane, and
microdialysis probes were inserted into the basolateral amygdala and neostriatum. After a twohour
stabilization period, four 30-min samples were collected. Thereafter, the treatment (vehicle,
composed of a viscous castor oil mixture (M et P Pharma AG, Stans, Switzerland; 0.5, 1.0 or 2.0
mg/kg of progesterone) was applied in a volume of 10µl (5 µl in each nostril). In other animals, a
subcutaneous injection of progesterone (1.0, 2.0 or 4.0 mg/kg) or vehicle (sesame oil) was given,
and samples were collected at 30 min interval for 4 h. Samples were immediately analyzed by
HPLC-ED. After the intranasal administration of 2mg/kg of progesterone there was an
immediate significant increase in dopamine in the basolateral amygdala. In the neostriatum, the
2mg/kg dose caused a delayed significant increase of dopamine. Subcutaneous administration of
4mg/kg of progesterone led to a delayed significant increase of dopamine, both, in the basolateral
amygdala and neostriatum, but smaller in magnitude in comparison with the intranasal treatment.
This is the first evidence of neurochemical action of progesterone on the basolateral amygdala.
We conclude that the intranasal route is more efficient in inducing an increase of dopaminergic
activity in the brain and that intranasally administered progesterone has differential effects on the
mesolimbic and nigrostriatal dopaminergic systems.