The substance P (SP) heptapeptide fragment SP1-7 alters the density of dopamine receptors in rat brain mesocorticolimbic structures during morphine withdrawal.

Qin Zhou, Anna M S Kindlundh, Mathias Hallberg, Fred Nyberg

Index: Peptides 25 , 1951-1957, (2004)

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Abstract

The aminoterminal fragment of substance P (SP), SP(1-7), has been suggested to modulate the expression of opiate tolerance and withdrawal behaviors in rodents. However, the mechanism of this effect is not yet clarified. Using a rat model we have previously demonstrated that SP(1-7) affects dopamine transmission and the expression of the dopamine D2-receptor gene transcript in the nucleus accumbens during naloxone precipitated morphine withdrawal. In the present study, we have applied autoradiography to investigate the effect of the heptapeptide on the binding of dopamine D1- and D2-receptors in mesocorticolimbic brain areas of male rats during morphine withdrawal. Morphine dependent animals were treated with an injection of SP(1-7) into the ventral tegmental area prior to naloxone challenge. The result indicated that the SP fragment elicited a significant decrease in specific binding to D1-like receptors in the caudate putamen, nucleus accumbens shell, nucleus accumbens core, substantia nigra and medial globus pallidus. Radioligand binding to dopamine D2-like receptors was also altered by SP(1-7). The heptapeptide induced a decreased density of these sites in the ventral tegmental area but an increased binding in the substantia nigra and the frontal cortex. The observed alterations in the D1- and D2-like receptor density could reflect activations in dopamine pathways associated with the above-mentioned brain regions. The result provides further evidence for the modulatory effect of SP(1-7) on dopamine systems during opioid withdrawal, suggesting the possible role for the heptapeptide to regulate morphine withdrawal reactions.