Differential effects of microinjections of d-amphetamine into the nucleus accumbens or the caudate putamen on the rat's ability to ignore an irrelevant stimulus.

Latent inhibition is an attentional process by which animals learn to ignore an irrelevant stimulus. Rats received either 0 or 30 preexposures to a tone which was later used as a conditioned stimulus (CS) in a two-way avoidance task. Tone preexposure resulted in retarded conditioning (i.e., latent inhibition) in animals which received microinjections of saline or amphetamine in the caudate-putamen and for those which received microinjections of saline in the nucleus accumbens. This latent inhibition effect, however, was not present in animals which received d-amphetamine microinjections in the nucleus accumbens. The failure of CS preexposure to retard conditioning in these animals was not due to drug-induced changes in either tone or shock sensitivity. The results are discussed in terms of the role of the mesolimbic dopamine system in learning to ignore an irrelevant stimulus and the use of LI as a possible animal model of the attentional deficit that seems to characterize some subpopulations of schizophrenic humans.

Effects of lactate on glucose metabolism of developing rat brain.

The effects of hyperlactatemia on cerebral glucose metabolism of normoglycemic 20-day-old rats were studied in animals breathing air or 20% CO2:21% O2:59% N2. Sodium lactate or sodium bicarbonate were given intraperitoneally, together with a mixture of [3H]deoxyglucose and [2-14C]glucose. Animals were sacrificed in a freeze-blowing apparatus at intervals of 2-15 min after injection. Blood lactate levels in the lactate-injected rats were 4-6 mM. Hyperlactatemia caused a gradual decline in the brain rate of glucose utilization in air-breathing animals to 50-70% of control rates. Results with both tracers were similar. Concentrations of Krebs cycle intermediates and glutamate did not decrease. These findings indicate that lactate can partially replace glucose as an oxidative fuel for developing rat brain. Hypercapnia depressed the rate of glucose utilization by developing brain and rates were 30-40% lower still in lactate-injected hypercapnic rats. Decreases in levels of Krebs cycle intermediates and glutamate were similar in both groups. Thus, lactate and CO2 are additive in their depressant effects on brain glucose utilization. The observation that lactate did not prevent the decreases in Krebs cycle intermediates and glutamate caused by hypercapnic acidosis suggests an inhibition of flux through pyruvate dehydrogenase during hypercapnia. The data from this study, coupled with data on lactate transport across the blood-brain barrier, indicate that the direction of movement of lactate and its rate of utilization by developing brain are functions of its concentration on blood relative to brain. Physiological and pathological conditions which elevate blood lactate levels above those in brain will, then, have a sparing effect upon brain glucose utilization.

An easily mass produced cannula system for chemical stimulation of the brain.

This paper describes a cannula system for chemical stimulation of the brain which can be easily mass produced in a reliable and inexpensive manner.

Axonal polypeptides cross-reactive with antibodies to neurofilament proteins.

Antibodies were prepared to mammalian CNS neurofilament proteins (NFPs) and the antibody specificities were compared using a sensitive immunoblotting method. This procedure was used to detect and characterize cross-reactive proteins and their degradation products in neurofilament preparations. NFPs were prepared by axon flotation. Rabbits were immunized with 200,000, 140,000, and 70,000 NFPs (200K, 140K, and 70K) that had been electrophoretically purified by polyacrylamide gel electrophoresis (PAGE). By immunohistofluorescence it was shown that all antisera stained similar filamentous structures in rat cerebellar neurons. By use of a horseradish peroxidase-conjugated indirect antibody procedure, however, differences were detected in the cross-reactivities of the antisera to rat NFPs, separated by PAGE and electrophoretically transferred to nitrocellulose membranes. Each antiserum exhibited strong binding to the homologous NFP and, thus, was suitable for the detection of cross-reactive polypeptides and proteolytic degradation products derived exclusively from the individual NFPs. Anti-200K, anti-140K, or anti-70K was applied to overloaded two-dimensional nitrocellulose blots of NFPs prepared by axon flotation. Each of the three sera detected a group of unique nonoverlapping polypeptides, some of which were identified as NFP degradation products. A different group of polypeptides was cross-reactive with antiserum to purified glial fibrillary acidic protein. The immunostaining of polypeptides on nitrocellulose was far more sensitive for detecting NFP degradation products than was staining polyacrylamide gels with Coomassie blue. Titers for the antisera were two to three orders of magnitude higher with the immunoblotting procedure than with immunohistologic methods. The sensitivity and the specificity of the described methods suggest their usefulness for examining proteolytic cleavage products of NFPs under a variety of conditions.