ANTIDEPRESSANTS &MONOAMINE RECEPTORS &RESPONSES

Project: Research project

Project Details

Description

The goals of this project are to determine: (1) if different types
of antidepressants alter the density and/or affinity of subtypes
of either beta adrenoceptors (BARs) or 5-HT-1 receptors either
throughout the brain or in localized areas; (2) how serotonergic
nerves alter the ability of antidepressants to decrease the density
of BARs; (3) factors involved in the regulation of central BARs in
vivo; and (4) if alterations in central receptors for certain
monamines occur in an animal model of depression. All experiments
will use rats and receptors will be visualized and quantified using
the technique of in vitro quantitative autoradiography. Many
antidepressants decrease the density of BARs and this
pharmacological effect has been speculated to be involved in their
clinical effects. The experiments proposed will evaluate if a
particular subtype of BAR is preferentially affected by
antidepressants and whether changes are produced in common areas
of the brain. In addition to affecting noradrenegic
responsiveness, antidepressants change both electrophysiological
and behavior responses elicited by serotonin (5-HT) agonists. The
responses altered have been linked to subtypes of a receptor for
5-HT, termed the 5-HT-1 receptor. By using quantitative
autoradiography, it will be possible to determine whether
antidepressant-induced changes in these subtypes account for the
alterations in responsiveness. In the experiments involving
subtypes of BARs or 5-HT-1 receptors, rats will be given
antidepressant of different types for 21 days. Antidepressants
studied will be those that block selectively the uptake of
norepinephrine or serotonin or inhibit selectively type A or type
B monoamine oxidase. Serotonin neurons are involved in
antidepressant-induced decreases in the density of BARs. To study
this, the ability of either the antidepressant, desipramine, or the
beta-agonist, isoproterenol (ISO), to decrease the density of BARs
will be measured in intact rats or rats with lesions of central
serotonergic neurons. Lesions will be made with the neurotoxin,
5,7-dihydroxytryptamine, given not only intraventricularly but also
directly into areas containing noradrenegic cell bodies or nerve
terminals. Lesions with a neurotoxin for catecholaminergic nerves,
6-hydroxydopamine, will be made in separate groups of rats to
determine how central noradrenegic neurons influence the ability
of ISO to decrease the density of beta-1 adrenoceptors. In these
experiments, ISO will be given into the right lateral ventricle of
rats through a permanently indwelling cannula connected to an Alzet
minipump. This experiment will provide information about the
feasibility of using beta agonists as antidepressants. The status
pf central monoamine receptors will also be measured in rats
exposed to uncontrolled shock, as this may be an animal model of
depression.
StatusFinished
Effective start/end date9/15/766/30/99

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $167,824.00
  • National Institutes of Health: $127,606.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $155,160.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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