A multi-institutional collaborative study was conducted concerning the course of pregnancy and delivery and the incidence of abnormal infants delivered of epileptic women. Of 657 women receiving antiepileptic drugs, 73% delivered live infants, 14% had miscarriage or stillbirth, and 13% underwent induced abortion. In contrast to the above findings, 80% of 162 patients not receiving antiepileptic drugs delivered live infants and 4% had miscarriage or stillbirth. The latter outcome was significantly increased in the medicated patients. In this series, 63 (9.9%) of 638 live births were malformed, 55 (11.5%) being from medicated mothers and 3 (2.3%) from nonmedicated mothers. The incidence of fetal malformation in medicated mothers was thus five times as high as that in nonmedicated mothers. Cleft lip and/or palate and malformations involving the cardiovascular system were found frequently in the infants from medicated mothers. General background factors that might exert teratogenic effects on pregnant patients with epilepsy were studied, and the potential toxicity of antiepileptic drugs to the fetus was also analyzed. In this regard, consideration should be given to whether the patient has partial epileptic seizures, whether the patient herself exhibits any malformation, or whether her previous pregnancy resulted in an abnormal outcome. The incidence of fetal malformation was the highest (12.7%) in the medicated patients who had epileptic seizures during the pregnancy. It is presumed on the basis of the results of analysis of the data that a combination of more than three drugs and a daily dose greater than a certain minimal level is likely to produce malformed infants.

A preliminary double-blind controlled study on the prophylactic effect of carbamazepine on recurrent manic-depressive psychotics was conducted with 22 patients using an inert placebo in ten subjects as a control drug. Carbamazepine in the dosage of 200-600 mg was administered for 1 year. Among the 22 carbamazepine subjects, carbamazepine was found to be effective in 60% of the cases and inert placebo in 22.2% (U-test, P less than 0.10). It is suggested that carbamazepine is a useful drug for the prophylaxis of manic-depressive illness.

SUMMARY1. Intracellular recordings were made from the nucleus accumbens neurones in brain slices from rats previously treated with saline or methamphetamine.2. In neurones from both methamphetamine-and saline (control)-treated rats, dopamine (0-1 mM) produced three types of responses: a biphasic response consisting of an initial hyperpolarization followed by a depolarization, a monophasic hyperpolarization and a simple depolarization.3. Haloperidol (1,UM) reversibly suppressed both responses to dopamine; (-sulpiride (1 ,UM) selectively abolished the depolarization and prolonged the hyperpolarization. Forskolin (10 ,tM) and dibutyryl adenosine 3',5'-cyclic monophosphate (1 mM) mimicked the hyperpolarization. Both of the latter two substances were more effective in neurones from methamphetamine-treated rats than in neurones from control rats.4. In slices from methamphetamine-treated rats, the dose-response curve for the dopamine hyperpolarization was shifted to the left of that seen in neurones from control rats by a factor of approximately 100. The dose-response curve for the dopamine depolarization was shifted to the right about 10-fold in neurones from rats treated with methamphetamine.5. In slices from control rats, dopamine (s< 0.1 mM) and methamphetamine (. 1 ,UM) had no effect on the EPSPs evoked by focal electrical stimulation of the periaccumbens regions: dopamine (>10 nM) and methamphetamine (1 UM) markedly depressed the EPSPs in slices from methamphetamine-treated rats. Depolarizations evoked by application of exogenous glutamate were unaffected by dopamine (< 5 ,UM).6. In slices from methamphetamine-treated rats, dopamine ( > 10 nM), forskolin (> 1 /IM) and dibutyryl adenosine 3',5'-cyclic monophosphate (1 mM) depressed Ca2+-dependent spikes as well as the EPSPs. Haloperidol (1 ,tM) completely reversed the depressions of the EPSPs and Ca2+-dependent spikes by dopamine, while (-sulpiride (1 LlM) was only partially effective.7. These results indicate that chronic methamphetamine administration leads to

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