Neurochemical mechanisms involved in behavioral effects of amphetamines and related designer drugs.

The motor activation produced by psychomotor stimulants has been long associated with the midbrain dopamine systems. While focused stereotyped behavior produced by high doses of indirect sympathomimetics is blocked by removal of dopamine terminals in the corpus striatum (Creese and Iversen 1975), the locomotor activation produced by low doses of indirect sympathomimetics is blocked by removal of dopamine terminals in the region of the nucleus accumbens (Kelly et al. 1975). This dopaminergic substrate for psychostimulant effects appears selective for the indirect sympathomimetics in that dopamine lesions to the region of the nucleus accumbens do not block caffeine, scopolamine, heroin, or CSF-induced locomotor activation (Swerdlow and Koob 1985; Vaccarino et al. 1986). The neurochemical sites for psychomotor stimulant reward are likely to be the presynaptic dopamine terminals located in the region of the nucleus accumbens, frontal cortex, and other forebrain structures that originate in the ventral tegmental area. Note, however, that intracranial self-administration of cocaine is elicited from the frontal cortex, but not from the nucleus accumbens (Goeders and Smith 1983). Thus, concomitant activation of structures other than the nucleus accumbens may be an important part of the circuitry involved in initiation of cocaine intravenous self-administration, as has been hypothesized for the opiates (Smith and Lane 1983; Smith et al. 1982). In addition, these neuropharmacological studies provide evidence to show that, in the rat, the neural/neurochemical substrates for processing the reinforcing and stimulant properties of psychomotor stimulants may be similar, if not identical. Parallel manipulations using dopamine receptor antagonists and 6-OHDA lesions produce parallel results. How far this parallelism continues in further processing is under current investigation; however, such an overlap brings additional impetus to earlier hypotheses relating reinforcement and motor function (Glickman and Schiff 1967). The motor activation produced by MDMA and MDE has similarities to classic psychostimulants, but also some important differences. In the BPM system, the stimulant-like properties of these drugs were reflected in significant increases in horizontal locomotor activity measured across a wide dose range. Interestingly, medium to high doses of MDMA or MDE produced a transient decrease in horizontal locomotion for the first 10 minutes, followed by a sustained increase. The increase in holepokes and rearings that typically accompanies the increase in ambulation seen with amphetamine itself or other indirect sympathomimetics (Geyer et al. 1986) was not observed with MDMA or MDE.(ABSTRACT TRUNCATED AT 400 WORDS)