The early appearance of monoamine systems in the developing mammalian
CNS suggests that they play a role in neural development. We review da
ta from two model systems that provide compelling new evidence of this
role. In one model system - in utero exposure to cocaine - specific a
nd robust alterations are seen in dopamine-rich areas of the cerebral
cortex, such as the anterior cingulate cortex: D-1 receptor-G protein
coupling is greatly reduced, the GABAergic system is altered and pyram
idal dendrites undergo excessive growth. In a second model system - a
transgenic mouse line in which the gene that encodes monoamine oxidase
A (MAOA) is disrupted, resulting in excessively high 5-HT levels - ba
rrels fail to form in the developing somatosensory cortex. Both models
reveal the effects of very early manipulation of monoamines on forebr
ain development, and the long-term anomalies that persist into adultho
od.