A significant fraction of infants born to mothers taking selective serotonin reuptake inhibitors (SSRIs) during late pregnancy display clear signs of antidepressant withdrawal indicating that these drugs can penetrate fetal brain in utero at biologically significant levels. Previous studies in rodents have demonstrated that early exposure to some antidepressants can result in persistent abnormalities in adult behavior and indices of monoaminergic activity. Here, we show that chronic neonatal (postnatal days 8-21) exposure to citalopram (5 mg/kg, twice daily, s.c.), a potent and highly selective SSRI, results in profound reductions in both the rate-limiting serotonin synthetic enzyme (tryptophan hydroxylase) in dorsal raphe and in serotonin transporter expression in cortex that persist into adulthood. Furthermore, neonatal exposure to citalopram produces selective changes in behavior in adult rats including increased locomotor activity and decreased sexual behavior similar to that previously reported for antidepressants that are nonselective monoamine transport inhibitors. These data indicate that the previously reported neurobehavioral effects of antidepressants are a consequence of their effects on the serotonin transporter. Moreover, these data argue that exposure to SSRIs at an early age can disrupt the normal maturation of the serotonin system and alter serotonin-dependent neuronal processes. It is not known whether this effect of SSRIs is paralleled in humans; however, these data suggest that in utero, exposure to SSRIs may have unforeseen long-term neurobehavioral consequences.

Neural ensemble processing of sensorimotor information during behavior was investigated by simultaneously recording up to 48 single neurons at multiple relays of the rat trigeminal somatosensory system. Cortical, thalamic, and brainstem neurons exhibited widespread 7- to 12-hertz synchronous oscillations, which began during attentive immobility and reliably predicted the imminent onset of rhythmic whisker twitching. Each oscillatory cycle began as a traveling wave of neural activity in the cortex that then spread to the thalamus. Just before the onset of rhythmic whisker twitching, the oscillations spread to the spinal trigeminal brainstem complex. Thereafter, the oscillations at all levels were synchronous with whisker protraction. Neural structures manifesting these rhythms also exhibited distributed spatiotemporal patterns of neuronal ensemble activity in response to tactile stimulation. Thus, multilevel synchronous activity in this system may encode not only sensory information but also the onset and temporal domain of tactile exploratory movements.

Anterograde tracers, Phaseolus vulgaris leucoagglutinin (PHA-L) and horseradish peroxidase (HRP), were used to study the thalamocortical afferents of the posteromedial barrel subfield (PMBSF) in rat primary somatosensory cortex (SI) at both light- and electron-microscopic levels. The PMBSF, also known as the barrel cortex, can be subdivided into barrel and interbarrel areas on the basis of cytoarchitectonic characteristics. Restricted injections confined to either the ventroposterior medial (VPM) or the rostral part of the posterior (Pom) nucleus allowed us to study and compare their projection patterns to the barrel cortex. We found that the interbarrel area receives inputs exclusively from the Pom, whereas the barrel area receives inputs from both the Pom and VPM. The laminar distributions of these two projections are largely segregated. After an injection of PHA-L or HRP into the VPM, labeled bouton-like swellings are found in layer VI and in layers IV through I of the barrel area, with the highest concentration in layer IV. On the other hand, after an injection of PHA-L or HRP into the Pom, labeled bouton-like swellings are distributed from upper layer V to layer I of the interbarrel area, as well as in layers V and I of the barrel area. Ultrastructural analysis showed that labeled bouton-like swellings of the VPM and the Pom pathways make synaptic contacts onto cortical neurons, and that these contacts are asymmetrical. Therefore, the VPM and the Pom projections are complementary to each other in the barrel cortex, and together they provide thalamic inputs to most layers of both the barrel and interbarrel areas. The differential patterns of terminations of the VPM and the Pom projections in the barrel cortex suggest that they may be involved in different types of cortical processing. Furthermore, our present findings may provide the anatomical basis for two parallel thalamocortical pathways, which previous physiological studies have indicated are each concerned with particular submodalities of somatic information.

Chronic treatment with the selective adenosine A 3 receptor agonist N 6 -(3-iodobenzyl)adenosine-5'-N-methylcarboxamide (IB-MECA) administered prior to either 10 or 20 min forebrain ischemia in gerbils resulted in improved postischemic cerebral blood circulation, survival, and neuronal preservation. Opposite effects, i.e., impaired postischemic blood flow, enhanced mortality, and extensive neuronal destruction in the hippocampus were seen when IB-MECA was given acutely. Neither adenosine A 1 nor A 2 receptors are involved in these actions. The data indicate that stimulation of adenosine A 3 receptors may play an important role in the development of ischemic damage, and that adenosine A 3 receptors may offer a new target for therapeutic interventions.