Third, heterosynaptic modulation of nonmonoamine transmitter release mediated by presynaptic monoamine receptors is augmented. It is interesting to note that all of the observations made in the VTA using low concentrations of cocaine, when applied acutely, center on the inhibition of the 5-HT transporter. Neurons originating in the VTA are thought to play a key role in the formation of addictive behaviors. Thus, the effects of cocaine on the membrane properties and synaptic potentials on neurons in this area are critical to understanding the cellular effects of this drug. There are at least three different populations of VTA neurons identified by the different synaptic potentials and the response to dopamine, 5-HT, and opioids.
Cocaine dramatically changes monoamine- mediated synaptic transmission.
The darker shaded area indicates the area over which 5-HT diffuses following release under control conditions. The lighter shaded area indicates that the spread of 5-HT is dramatically increased following the blockade of the SERT with cocaine. In this case cocaine decreased the amplitude of the GABAb IPSP without changing the timecourse. Thus, one more effect of low concentrations of cocaine in the VTA is to inhibit GABA release. This effect of cocaine would be expected to result in disinhibition of dopamine cells to increase the release of dopamine.