Ma. Klitenick et Pw. Kalivas, BEHAVIORAL AND NEUROCHEMICAL STUDIES OF OPIOID EFFECTS IN THE PEDUNCULOPONTINE NUCLEUS AND MEDIODORSAL THALAMUS, The Journal of pharmacology and experimental therapeutics, 269(1), 1994, pp. 437-448
The brain circuitry mediating spontaneous and psychostimulant-induced
locomotion comprises, in part, connections between the ventral tegment
al area, nucleus accumbens and ventral pallidum. Two primary efferent
projections from the ventral pallidum are to the mediodorsal thalamic
nucleus (MD) and the pedunculopontine nucleus (PPN), including the mes
encephalic motor area. To assess the functional role of the PPN and MD
in this motor circuit, the behavioral and neurochemical effects of in
tra-PPN and intra-MD administration of the mu opioid receptor agonist
Tyr-D-Ala-Gly-MePhe-Gly(ol) (DAMGO) were examined. Bilateral microinje
ctions of DAMGO into either the PPN or MD elicited a dose-dependent in
crease in motor activity which was blocked by pretreatment with naloxo
ne (2.0 mg/kg i.p.). Three studies were conducted to evaluate a role f
or mesoaccumbens dopamine transmission in DAMGO-induced motor activity
. Systemic administration of the dopamine antagonist, heloperidol(0.1
mg/kg i.p.) produced a partial antagonism of the motor effect elicited
by DAMGO in the MD, but abolished the response to DAMGO in the PPN. I
nhibition of dopamine neurons by microinjecting the gamma-aminobutyric
acid(B) agonist, baclofen (0.15 nmol/side), into the ventral tegmenta
l area attenuated the motor activity elicited by DAMGO in the PPN but
was without effect on DAMGO in the MD. Finally, microdialysis revealed
that DAMGO microinjection into either the PPN or MD elicited a dose-r
elated increase in extracellular dopamine content in the nucleus accum
bens. However, only after DAMGO in the PPN were extracellular levels o
f dopamine metabolites increased. These results demonstrate that the m
otor stimulant response to DAMGO in the PPN is dopamine dependent and
involves stimulation of mesoaccumbens dopamine neurons. In contrast, t
he motor response by DAMGO in the MD only partly involves dopaminergic
mechanisms, perhaps via a presynaptic action because the effect was n
ot altered by inhibiting impulse flow in mesoaccumbens dopamine neuron
s with baclofen.