AJP - Regulatory, Integrative and Comparative Physiology, Vol 251, Issue 2 243-R249, Copyright © 1986 by American Physiological Society
Endogenous enkephalin modulation of dopamine neurons in ventral tegmental area
P. W. Kalivas and R. Richardson-Carlson
Many lines of evidence support the possibility that the opioid
pentapeptides Met- and Leu-enkephalin can modulate dopamine neurons in the
ventral tegmental area (VTA). Thus microinjection of enkephalin analogues
into the VTA of rats produces a dopamine-dependent increase in spontaneous
motor activity and an increase in dopamine metabolism in certain mesolimbic
dopamine terminal fields, such as the nucleus accumbens. To determine if
these effects can be produced by endogenous enkephalins, an enkephalinase A
inhibitor, thiorphan, was microinjected into the VTA to inhibit enkephalin
metabolism. Thiorphan produced a dose-dependent (0.3-3.33 micrograms)
increase in spontaneous motor activity that was blocked by pretreatment
with the opioid antagonist naloxone (2.0 mg/kg ip) or the dopamine
antagonist haloperidol (0.1 mg/kg ip). Thiorphan injection into the VTA
increased dopamine metabolism in the nucleus accumbens, prefrontal cortex,
and septum but not in the striatum. In all brain regions the increase in
dopamine metabolism was blocked by pretreatment with naloxone. These data
demonstrate that endogenous enkephalin in the VTA can increase the activity
of A10 dopamine neurons, supporting a physiological role for enkephalin in
mesolimbic and mesocortical dopamine-mediated behaviors.
