Postnatal stress selectively upregulates striatal N-methyl-D-aspartate receptors in male rats.

Early life events have been thought to contribute towards vulnerability to drug addiction later in life. In the present investigation, the effect of daily neonatal maternal isolation stress on NMDA channel activity was studied. [3H]MK-801 binding was measured in several brain regions from neonatally isolated (ISO) and nonhandled (NH) adult male and female rats. Maximal [3H]MK-801 binding in the caudate-putamen of male ISO rats was 58% higher compared to same sex NH rats. Unlike male rats, maximal [3H]MK-801 binding in the caudate-putamen of female ISO rats was lower than female NH rats. No other brain region showed any significant difference in maximal [3H]MK-801 binding between ISO and NH male and female rats, respectively. There was no effect of pup isolation on the binding affinity (K(d) value) in either sex. Repeated maternal isolation is associated with alterations in the NMDA channel activity in the caudate-putamen of adult rats, and may be responsible for the augmentation in the addictive behavior reported.

L- and D- methionine provide equivalent long term protection against CDDP-induced ototoxicity in vivo, with partial in vitro and in vivo retention of antineoplastic activity.

Treatment of metastatic tumors with ionic platinum compounds is hampered by the potent nephrotoxic, ototoxic and neurotoxic properties of these drugs. Recent studies have shown that sulfur-containing antioxidants relieve the dose limiting side effects of cis-diamminedichloroplatinum (CDDP), the most commonly used ionic platinum therapy. Here we report that both isomers of the sulfur-containing antioxidant methionine (MET) completely block the in vivo ototoxic and nephrotoxic effects of CDDP, and the duration of MET otoprotection is longer than has been previously reported. Rats treated with either L- or D-MET in addition to CDDP exhibited no signs of auditory system damage after 7 days, as evaluated by the auditory brainstem response and scanning electron microscopic examination of the organ of Corti, while CDDP-treated rats exhibited pronounced evidence of ototoxic damage after only 3 days. Microscopic examination of kidney tissue revealed moderate to severe nephrotoxic damage to CDDP-treated rats after 5 days, while rats co-treated with either MET isomer showed no evidence of kidney damage. Mortality among CDDP-treated subjects increased steadily over the period of the study, while all of the MET-protected rats survived. Finally, the efficacy of CDDP in the presence of L- or D-MET was evaluated in vitro using cultures of MTLN-3 breast tumor cell lines, and in vivo using implanted MTLN-3 tumors. Both L- and D-MET reduced the ability of CDDP to kill tumor cells in vitro and in vivo, however, our data suggest that a higher proportion of the antineoplastic activity of CDDP is retained in the presence of L- MET.

Normal time course of auditory recognition in schizophrenia, despite impaired precision of the auditory sensory ("echoic") memory code.

Prior studies have demonstrated impaired precision of processing within the auditory sensory memory (ASM) system in schizophrenia. This study used auditory backward masking to evaluate the degree to which such deficits resulted from impaired overall precision versus premature decay of information within the short-term auditory store. ASM performance was evaluated in 14 schizophrenic participants and 16 controls. Schizophrenic participants were severely impaired in their ability to match tones following delay. However, when no-mask performance was equated across participants, schizophrenic participants were no more susceptible to the effects of backward maskers than were controls. Thus, despite impaired precision of ASM performance, schizophrenic participants showed no deficits in the time course over which short-term representations could be used within the ASM system.

Organizing principles of cortical integration in the rat neostriatum: corticostriate map of the body surface is an ordered lattice of curved laminae and radial points.

The neuroanatomic organizing principles underlying integrative functions in the striatum are only partially understood. Within the three major subdivisions of the striatum-sensorimotor, associative, and limbic--longitudinal zones of axonal plexuses from the cerebral cortex end in bands and clusters that innervate cell groups. To identify organizing principles of the corticostriate bands and clusters, we localized somatosensory cortical cells receptive to light touch on the hindlimb, forelimb, or vibrissae by extracellular recording, and we labeled their projections by iontophoretic application of dextran anterograde tracers. The results show that cortical cells in columnar groups project to the striatum in the form of successive strips, or laminae, that parallel the curve of the external capsule. The vibrissae somatosensory cortex projects to the most lateral lamina. Just medial to the vibrissae projection, the major axonal arborizations arising from hindlimb and forelimb somatosensory cortex are organized within a common lamina, where they interdigitate and overlap as well as remain separate. In addition, the hindlimb and forelimb cortex send small projections to the vibrissae lamina, and vice versa, forming broken, radially oriented lines of points across the laminar strips. The major somatosensory projections are in the dorsolateral, calbindin-poor sensorimotor striatum, whereas the radially oriented projection points extend into the medial, calbindin-rich associative striatum. Extending previous studies of corticostriate projections, this report shows a grid translation of columnar somatosensory cortical inputs into striatum and a detailed map for the rat sensorimotor zone. The lattice-like grid is a novel functional/neuroanatomic organization that is ideal for distributing, combining, and integrating information for sensorimotor and cognitive processing.