Facilitation of GABA release by neurotensin is associated with a reduction of dopamine release in rat nucleus accumbens.
The main aim of the present study was to investigate the effects of local perfusion with the tridecapeptide neurotensin on extracellular GABA and dopamine levels in the nucleus accumbens of the halothane-anaesthetized rat, using in vivo microdialysis. In an initial set of characterization studies we examined the Na+ dependence of neurotransmitter release by local perfusion with ouabain, veratridine and tetrodotoxin. Local perfusion with the Na+ ATPase inhibitor ouabain (10 microM) or the Na+ channel agonist veratridine (20 microM) perfused into the nucleus accumbens increased both extracellular GABA and dopamine levels. The Na+ channel antagonist tetrodotoxin (1 microM) consistently decreased (24% of basal) dopamine levels, while even at 10 microM it did not affect GABA. However, tetrodotoxin (10 microM) abolished the veratridine-induced increase in both GABA and dopamine, demonstrating that Na(+)-dependent neuronal activity is involved in this release mechanism. In a second set of experiments a hypothesis for a functional link between neurotensin, dopamine and GABA in the medial nucleus accumbens was tested. Towards this aim, the effects of local perfusion with a high 1 microM concentration of neurotensin into the nucleus accumbens increased both GABA (210% of basal value) and dopamine (145% of basal) release. However, a low (10 nM) concentration of neurotensin again increased GABA release (160% of basal), but decreased that of dopamine (75% of basal value). Furthermore, the local perfusion with the GABAA receptor antagonist bicuculline abolished the neurotensin (10 nM) induced inhibition of dopamine release without affecting the increase in GABA release. These findings suggest that neurotensin modulates both GABA and dopamine neurotransmission in the nucleus accumbens.(ABSTRACT TRUNCATED AT 250 WORDS)
Tanganelli
S
S
Department of Pharmacology, University of Ferrara, Italy.
O'Connor
W T
WT
Ferraro
L
L
Bianchi
C
C
Beani
L
L
Ungerstedt
U
U
Fuxe
K
K
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000032:analysis; D008297:Male; D017551:Microdialysis; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009496:Neurotensin / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000502:physiology; D015222:Sodium Channels / Q000187:drug effects; D013047:Specific Pathogen-Free Organisms; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D015222:Sodium Channels; D015102:3,4-Dihydroxyphenylacetic Acid; D009496:Neurotensin; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D010042:Ouabain; D014701:Veratridine; D012964:Sodium; D004298:Dopamine; D006719:Homovanillic Acid; D001640:Bicuculline