To be sure, numerous other systems, from the main excitatory and inhibitory, glutamate and GABA, to virtually all neurobiological systems, are likely to be included as well. Afferents of both glutamate and GABA systems modulate the activity of dopaminergic neurons in the VTA (Giorgetti et al., 2002), and metabotropic glutamate receptors interact with dopaminergic neurotransmission in the nucleus accumbens (rev. in Breysse et al., 2002)—both regions integral to the dopaminergic circuitry. Stimulation of the GABAA receptors leads to an increase in dopaminergic activity, whereas activation of GABAB receptors results in its decrease (Goudreau et al., 1994; Kalivas et al., 1990). In addition to their role in behavior regulation, the GABA- and glutamatergic systems massively contribute to drug response. For instance, the activation of serotonergic axons in the hypothalamus causes the release of metenkephalin in the VTA, which suppresses the release of GABA. This results in dopamine release in the nucleus accumbens and hippocampus. Opioid receptor agonists increase extracellular dopamine levels within the nucleus accumbens by disinhibiting GABA interneurons in the VTA (Johnson and North, 1992). Benzodiazepines and barbiturates affect GABA
