Intraaccumbens injections of substance P, morphine and amphetamine: effects on conditioned place preference and behavioral activity.

The nucleus accumbens of the rat plays a critical role in behavioral activation and appetitive motivation. Within the nucleus accumbens, the shell subarea may be especially relevant, since this site is anatomically related to other brain areas that are considered to play a critical role in the processing of motivation. We investigated the behavioral effects of local drug treatments aimed at the shell of the nucleus accumbens and tested the indirect dopamine agonist d-amphetamine, the opiate agonist morphine, and the neurokinin substance P. These substances are known to exert positive reinforcing effects, and can affect behavioral activity; effects that are physiologically closely related to the nucleus accumbens and its inputs and outputs. Our results show that unilateral microinjections of amphetamine (1.0 microg, 10.0 microg) into the shell of the nucleus accumbens dose-dependently stimulated behavioral activity (locomotion, rears, sniffing), and led to conditioned place preference. Furthermore, the effect of amphetamine on place preference was negatively related to the psychomotor stimulant action on rears. Morphine injections (5.0 microg) also stimulated behavioral activity and elicited contraversive turning, but were ineffective with respect to place preference. Finally, the neuropeptide substance P, injected in a dose range of 0.1-10.0 ng, had no significant behavioral effects. These findings are discussed with respect to the role of dopaminergic, peptidergic and cholinergic mechanisms in the nucleus accumbens. It is suggested that dopamine, opiates, and neurokinins in the shell of the nucleus accumbens are differentially involved in mediating behavioral activity and appetitive motivation.