Neurochemical and electrophysiological disturbances mediate developmental behavioral alterations produced by...

Many centrally acting drugs which are prescribed for hypertension, depression, epilepsy, insomnia and asthma may also affect fetal brain neurotransmission and behavioral states. Nearly all these drugs enter the fetal circulation following maternal administration. The immaturity of the blood-brain barrier and greater accumulation in the developing brain make the fetal brain a major target of its mother's medication. Adverse effects that are seen in the fetus are not necessarily evident in its mother. We have shown that drugs like clonidine (an antihypertensive) and clomipramine (an antidepressant), which act on noradrenaline and serotonin neurotransmission in the brain, suppress rapid eye movement sleep in the developing rat. In adulthood, the neonatally treated rats showed hyperactivity, hyperanxiety, reduced sexual behavior, disturbed sleep patterns and reduced cerebral cortical size. Furthermore, such treatment induced an increase in voluntary alcohol consumption and a decreased adaptability of responses to changes in water deprivation in a Y-maze. Little is known about long-lasting consequences of centrally acting drugs used during late gestation in humans. Minor neurological disturbances, such as delayed visual motor performance, smaller head circumference, increased anxiety and disturbed sleep-wake patterns, have been reported in children born to hypertensive mothers treated with clonidine or alpha-methyl-dopa.