Abstract
While
most drugs of abuse increase dopamine neurotransmission, rapid
neurochemical measurements show that different drugs evoke distinct
dopamine release patterns within the nucleus accumbens. Rapid changes in
dopamine concentration following psychostimulant administration have
been well studied; however, such changes have never been examined
following opioid delivery. Here, we provide novel measures of rapid
dopamine release following intravenous infusion of two opioids, morphine
and oxycodone, in drug-naïve rats using fast-scan cyclic voltammetry
and rapid (1 min) microdialysis coupled with high-performance liquid
chromatography - tandem mass spectrometry (HPLC-MS). In addition to
measuring rapid dopamine transmission, microdialysis HPLC-MS measures
changes in GABA, glutamate, monoamines, monoamine metabolites and
several other neurotransmitters. Although both opioids increased
dopamine release in the nucleus accumbens, their patterns of drug-evoked
dopamine transmission differed dramatically. Oxycodone evoked a robust
and stable increase in dopamine concentration and a robust increase in
the frequency and amplitude of phasic dopamine release events.
Conversely, morphine evoked a brief (~ 1 min) increase in dopamine that
was coincident with a surge in GABA concentration and then both
transmitters returned to baseline levels. Thus, by providing rapid
measures of neurotransmission, this study reveals previously unknown
differences in opioid-induced neurotransmitter signaling. Investigating
these differences may be essential for understanding how these two drugs
of abuse could differentially usurp motivational circuitry and
powerfully influence behavior.
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