Sprout
Bluelight Crew
- Joined
- Oct 13, 2009
- Messages
- 7,377
Opposing tonically active endogenous opioid systems modulate the
mesolimbic dopaminergic pathway.
[RAINER SPANAGEL, ALBERT HERZ, AND TONI S. SHIPPENBERG
Department of Neuropharmacology, Max Planck Institute for Psychiatry, D-8033 Martinsried, Federal Republic of Germany]
ABSTRACT The mesolimbic dopaminergic system has
been implicated in mediating the motivational effects of oploids
and other drugs of abuse. The site of action of opioids within
this system and the role of endogenous opioid peptides in
modulating dopamine activity therein remain unknown. Employing
the technique of in vivo microdialysis and the administration
of highly selective opioid ligands, the present study
demonstrates the existence of tonically active and functionally
opposing it and K opioid systems that regulate dopamine
release in the nucleus accumbens, the major terminal area of
A10 dopaminergic neurons. Thus, stimulation of J-type receptors
in the ventral tegmental area, the site of origin of A10
dopminergic neurons, increases dopamine release whereas the
selective blockade of this opioid receptor type results in a
significant decrease in basal dopamine release. In contrast,
stimulation of K-type receptors within the nucleus accumbens
decreases dopamine release whereas their selective blockade
markedly increases basal dopamine release. These data show
that tonic activation of pA and ic receptors is required for the
maintenance of basal dopamine release in the nucleus accumbens.
In view of the postulated role of the mesolimbic system in
the mediation of drug-induced alterations in mood and affect,
such findings may have implications for the treatment of opiate
dependence and affective disorders.
mesolimbic dopaminergic pathway.
[RAINER SPANAGEL, ALBERT HERZ, AND TONI S. SHIPPENBERG
Department of Neuropharmacology, Max Planck Institute for Psychiatry, D-8033 Martinsried, Federal Republic of Germany]
ABSTRACT The mesolimbic dopaminergic system has
been implicated in mediating the motivational effects of oploids
and other drugs of abuse. The site of action of opioids within
this system and the role of endogenous opioid peptides in
modulating dopamine activity therein remain unknown. Employing
the technique of in vivo microdialysis and the administration
of highly selective opioid ligands, the present study
demonstrates the existence of tonically active and functionally
opposing it and K opioid systems that regulate dopamine
release in the nucleus accumbens, the major terminal area of
A10 dopaminergic neurons. Thus, stimulation of J-type receptors
in the ventral tegmental area, the site of origin of A10
dopminergic neurons, increases dopamine release whereas the
selective blockade of this opioid receptor type results in a
significant decrease in basal dopamine release. In contrast,
stimulation of K-type receptors within the nucleus accumbens
decreases dopamine release whereas their selective blockade
markedly increases basal dopamine release. These data show
that tonic activation of pA and ic receptors is required for the
maintenance of basal dopamine release in the nucleus accumbens.
In view of the postulated role of the mesolimbic system in
the mediation of drug-induced alterations in mood and affect,
such findings may have implications for the treatment of opiate
dependence and affective disorders.
