OPIOID EFFECTS ON NUCLEUS BASALIS CHOLINERGIC NEURONS

Project: Research project

Description

The LONG TERM OBJECTIVE of this application is to better understand the
biological basis of narcotic abuse. Morphine is a potent reinforcer, a
manifestation of the drug interacting with brain opioid receptors. The
ventral pallidum/nucleus basalis (VP/nB) is rich with opioid binding sites.
A major neuronal population of the VP/nB is the acetylcholine-containing
cells and these cells exhibit conditioning-related responses to stimuli
preceding reinforcement. Enkephalinergic terminals make synaptic contact
with VP/nB cholinergic neurons; however, the functional consequences of
this interaction is largely unknown. HYPOTHESIS: Enkephalinergic inputs
to VP/nB cholinergic neurons mediate aspects of reinforcement. Proposed
SPECIFIC AIMS: I. To characterize the pharmacology and physiology of enkephalinergic
projections to the VP/nB. Putative cholinergic neurons will be
electrophysiologically characterized in vivo, and the synaptic pharmacology
of opioid receptors will be evaluated using microiontophoretic application
of receptor-specific opioid agonists and antagonists. Hemicholinium
binding, which is indicative of cholinergic activity, will be used to
assess cholinergic terminal function after intra-VP/nB microinjection of
the opioid agents. II. To study the involvement of VP/nB neurons and opioid receptors in the
abuse potential of narcotics. The reinforcing properties of receptor-
specific opioid agonists microinjected into the VP/nB will be assessed
using a condition place preference paradigm. Electrophysiologic recordings
in behaving rats will examine single-unit activity recorded from the VP/nB
while the animal is in an environment previously paired with morphine
(CS+), or paired with vehicle (CS-). Comparisons also will be made between
neuronal firing and the animals' spontaneous behavior. To determine if
tolerance develops to the above parameters, experiments will be conducted
in rats chronically treated with morphine. VP/nB cholinergic neurons are involved with reinforcement, and yet these
cells have not been investigated with regard to the neurobiological
mechanisms underlying opioid abuse. Results obtained in the proposed
experiments should impart needed information on the neurobiology of the
VP/nB, and also provide significant information useful in devising
appropriate pharmacological strategies for the treatment of narcotic abuse.
StatusFinished
Effective start/end date10/1/852/28/06

Funding

  • National Institutes of Health

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Neprilysin
Cholinergic Neurons
Opioid Receptors
Morphine
Opioid Analgesics
Opioid-Related Disorders
Cholinergic Agents
Pharmacology
Animal Behavior
Globus Pallidus
Narcotic Antagonists
Neurobiology
Narcotics
Presynaptic Terminals
Microinjections
Acetylcholine
Binding Sites
Neurons
Brain
Pharmaceutical Preparations

ASJC

  • Medicine(all)