Attempts to determine the neural circuitry where addictive drugs act to establish drug-seeking habits are aided by dual-probe dialysis mapping studies in which drug is infused through a cannula at one site and the consequences for neurotransmitter release at that site and at some distal, presumably linked, site. In the past year we have used this approach to studying the underlying the habit-forming effects of phencyclidine (PCP). It is known from intracranial self-administration studies that PCP's rewarding actions are triggered in nucleus accumbens and medial prefrontal cortex. We studied the effects of nucleus accumbens and ventral tegmental PCP infusions on activity of the mesocorticolimbic dopamine system. PCP in nucleus accumbens caused dopamine release in the ventral tegmental area, nucleus accumbens, and prefrontal cortex. PCP in the ventral tegmental area or prefrontal cortex affected dopamine levels only locally. PCP in nucleus Accumbens decreased GABA levels in nucleus accumbens and ventral tegmental area. MK-801, which shares PCP's ability to block NMDA receptors but not PCP's ability to block dopamine uptake, mimicked the effects of PCP when injected into nucleus accumbens. These data suggest that it is PCP's direct action on GABAergic neurons of nucleus accumbens that accounts for the drug's addiction liability.
