Effects of intranigral substance P and neurokinin A on striatal dopamine release--II. Interactions with bicuculline and naloxone.
The functional roles of striatonigral neurokinins were studied by analysing the effects of intranigral injections of substance P and neurokinin A on the extracellular levels of dopamine and dihydroxyphenylacetic acid in the striatum, as measured by in vivo microdialysis in rats. An opioid antagonist, naloxone, and a GABAergic antagonist, bicuculline, were tested and analysed for their ability to modify the neurokinin effects. Unilateral injections of substance P (0.07 nmol) or neurokinin A (0.09 nmol) into the substantia nigra, pars reticulata of halothane anaesthetized rats produced long-lasting increases in ipsilateral striatal dopamine and dihydroxyphenylacetic acid levels. Intranigral injections of naloxone (30 and 300 nmol) produced short-lasting decreases in striatal dopamine, concomitant with an increase in dihydroxyphenylacetic acid. Intranigral injections of 7.0 nmol bicuculline produced an increase, while 70 nmol produced a decrease in striatal dopamine, however, both doses produced an increase in dihydroxyphenylacetic acid. When co-administered intranigrally, the high dose of naloxone (300 nmol) completely blocked the dopamine stimulation of substance P (0.07 nmol), but only moderately inhibited that of neurokinin A (0.09 nmol). The high dose of bicuculline (70 nmol) completely blocked the dopamine stimulation of neurokinin A, but only moderately inhibited that of substance P. Naloxone (30 and 300 nmol) enhanced the dihydroxyphenylacetic acid response to substance P, while bicuculline (70 nmol) inhibited the dihydroxyphenylacetic acid response to neurokinin A. These findings complement and extend the findings in the preceding paper, demonstrating that intranigral substance P and neurokinin A stimulate striatal dopamine via different neuronal mechanisms. We suggest that opioid drugs have a greater influence over substance P while GABAergic drugs have a greater influence over neurokinin A.
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
M S
MS
Reid
M
M
Herrera-Marschitz
U
U
Ungerstedt
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology*; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004338:Drug Combinations; D004347:Drug Interactions; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D015288:Neurokinin A / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013373:Substance P / Q000378:metabolism / Q000502:physiology*; D013378:Substantia Nigra / Q000378:metabolism*
D004338:Drug Combinations; D013373:Substance P; D009270:Naloxone; D015288:Neurokinin A; D004298:Dopamine; D001640:Bicuculline