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Eur J Neurosci. 2002 Jan;15(2):257-68.

Mu and kappa opioid agonists modulate ventral tegmental area input to the ventral pallidum.

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Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago Stritch School of Medicine, Building 102, 2160 South First Avenue, Maywood, IL 60153, USA.


The ventral pallidum (VP) is situated at the convergence of midbrain dopamine and accumbal opioid efferent projections. Using in vivo electrophysiological procedures in chloral hydrate-anaesthetized rats, we examined whether discrete application of mu- [D-Ala2,N-Me-Phe4,Gly-ol5 (DAMGO)] or kappa- (U50488) opioid receptor agonists could alter VP responses to electrical stimulation of ventral tegmental area. Rate suppressions occurred frequently following ventral tegmental area stimulation. Consistent with an involvement of dopamine in this effect, none of the 12 spontaneously active ventral pallidal neurons recorded in rats that had monoamines depleted by reserpine responded to electrical stimulation of ventral tegmental area. Moreover, in intact rats, the dopamine antagonist flupenthixol attenuated evoked suppression in 100% of the neurons tested; however, the GABAA antagonist bicuculline was able to slightly attenuate the response in 50% of the neurons tested. These observations concur with our previous studies in indicating that ventral tegmental area stimulation releases dopamine (and sometimes GABA) onto ventral pallidal neurons. Both DAMGO and U50488 decreased the inhibitory effects of ventral tegmental area stimulation. These effects on the endogenously released transmitter differed from those seen with exogenously applied dopamine, for DAMGO did not alter the efficacy or potency of microiontophoretically applied dopamine. Taken together, these observations suggest that the interaction between DAMGO and dopamine does not occur at a site that is immediately postsynaptic to the dopaminergic input within the VP, but rather that opioid modulation involves mechanisms governing presynaptically released dopamine. These modulatory processes would enable ventral pallidal opioids to gate the influence of ventral tegmental area dopamine transmission on limbic system outputs at the level of the VP.

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