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A complementary Machine Learning disposition method was generated and tested for after develop inspections in lithography. For lithography coating defects, this new method showed twice the sensitivity and five times the specificity in a controlled experiment versus the baseline system. Applying the detection method along with process improvements, preventative measures and rework for splatter defects, reduced yield loss from splatters by over 30x. Herein we describe learnings on the use of image enhancement for training and disposition, an Explainable AI system to support understanding, and a process flow to train augmentation based on performance.

In rats, sectioning the fimbria-fornix leads to a decrease in cells reactive for acetylcholinesterase and choline acetyltransferase, as well as other types of cells, in the medial septal area that project to the hippocampus. In this study cells in the medial septal area were stained for acetylcholinesterase reaction product or by a Nissl method two weeks after unilateral section of the fimbria-fornix. Counts were made of cells on each side of the midline by independent observers. The counts of the cells on the two sides of the brain were compared in rats that had been given nimodipine (70 μg/kg) just after the lesion and for 7 additional days and in rats that had been given only the vehicle for an equivalent amount of time. The number of cells reactive for acetylcholinesterase was reduced in the medial septal area on the side of the brain in which the forebrain fornix was sectioned, but this occurred to a significantly less extent in the nimodipine-treated rats. No differences were noted in the number of cells on the two sides of the medial septal area when counted in Nissl-stained sections.

Male Wistar rats subjected to unilateral fimbria-fornix transection by mechanical knife cut or to sham operations were tested in a water maze and in an open field. Half the animals in each group were treated with either 0.06 mg/kg nimodipine or vehicle, administered i.p. for 7 days, beginning the day of surgery. Animals were sacrificed and brains were processed for acetylcholine esterase (AChE) histochemistry. In the water maze, lesioned rats showed a significant impairment relative to the sham-operated animals. Nimodipine treatment did not improve performance. There were no differences among the groups in the observed frequencies of the open field behaviors of locomotion, hole-poke, rearing and grooming. A significant reduction of AChE-positive cell bodies was found in the medial septal region on the side of the lesion. There were no differences in water maze performance among groups of rats treated with 0.0, 0.5, 1.0, or 5.0 mg/kg nimodipine for 7 days, beginning the day of fimbria-fornix transection, in an attempt to determine any dose-dependent effect of the drug.

This study investigated the effects of fetal rat umbilical cord compression on anatomical, biochemical, and behavioral parameters of development. Further, the study examined the ability of the calcium channel antagonist nimodipine to afford protection from this insult. Near the day of birth (E21), the umbilical cord of individual fetuses was not clamped or clamped for 2, 6, or 12 min. Before clamping, mothers were given 70 μg/kg (i.p.) nimodipine in a polyethylene glycol (PEG) vehicle or the vehicle alone. Selected animals were sacrificed for cytochrome oxidase histochemistry. The remainder of the pups were given to foster mothers and allowed to develop through adulthood. At the end of testing all animals were sacrificed and the brains weighed and measured. Histochemical analysis revealed that clamping resulted in a decrease in cytochrome oxidase reaction product in the hippocampus. The reduction in this marker of oxidative metabolism was not as pronounced in animals from drug-treated mothers. Alterations in behavior produced by clamping were detectable as early as the third day after birth (P3). At this age, pups subjected to cord clamping exhibited impaired righting and diminished avoidance of a 'cliff' on which they had been placed. On P67-P75, clamped animals exhibited hyperactivity in an open field, low rates of spontaneous alternation in a T-maze, and impaired learning and memory in a Pavlovian conditioned aversion-to-brightness test. The calcium channel blocker afforded protection from the effects of cord clamping, since the nimodipine-treated animals were less impaired in these behavioral tests. Animals that had been subjected to cord clamping showed reduced brain volumes and dimensions on P80. Nimodipine treatment normalized these parameters of brain development relative to non-clamped controls. Taken together, these results indicate that brief periods of umbilical cord occlusion near the time of birth can have both immediate and long-term effects on different parameters of development. In addition, the calcium channel blocker nimodipine affords partial protection from damage induced by compression of the fetal umbilical cord.

The data presented in this article are commensurate with the idea that in the not-too-distant future, pharmacologic interventions will be available to prevent many of the deleterious effects of brain damage due to hypoxia and other causes of global brain insult. It is also likely that even after highly localized brain damage, there will be specific interventions to reduce the usual mental and behavioral changes induced by the damage. While the specific experimental studies use adult animals, similar beneficial effects are being found in studies in which damage occurs in the perinatal period.

The IBM 300 mm wafer manufacturing line provides a case study for the optimization of an automated macro defect inspection system to accurately flag global wafer color variation. The IBM inspection system was falsely flagging a large number of wafers primarily for global wafer color variation, leading to unacceptable amounts of production volume being placed on hold. A review of the macro inspection system identified several areas for improvement. An investigation into the installed hardware base found a panel behind the beam splitter was introducing noise through reflected light. This panel was replaced with a less reflective material. A review of the failed wafers found that maximum light levels were not achieved across all tools and an improved diffuser plate for the fiber optic output was designed to improve light transmittance. Global wafer color is determined by comparing the scanned wafer image to a "golden" data set, referred to as a "color baselist," which is composed of data from 30 wafers. A review of the recipe baselists revealed that some of the wafer samples did not accurately represent process conditions, and new wafer samples were collected. Finally, a tool-to-tool matching test revealed that the set of weightings given to each of the color parameters in the baselists was not optimized. After implementing the above changes, false global wafer color failures were virtually eliminated.

This paper discusses the controls benefit accomplished on both product wafers and process tools at IBM's 300mm wafer manufacturing line by using integrated auto-macro defect inspection in all the photolithography tool clusters for after-develop-inspection (ADI). Inspection is supported on all production wafers (with possibility to sample wafers if desired). To get to this level of control the overall 'ADI process' in the line had to be first rendered manufacturable. Therefore, significant effort had to be focused towards decreasing false fails and nuisance holds. As a result, over the last year inspection software related false fails were reduced 3X, hardware related PC communication fails were decreased 5X, and fab automation related nuisance wafer holds were reduced 12X. Fail rate has been sustainable at 6% (± 2%) for over two quarters. At this point only 20% of the fail rate is false and is mostly attributable to hardware related wafer alignment issues during inspection. By decreasing false fails and hold rates, sensitivity and effectiveness in the line towards correctly reacting to real fail signals significantly improved. Product wafers with real fails are now consistently reacted to real-time in the line leading to rework and elimination of photo sector generated macro defects. Contribution of this integrated metrology system to fab rework rate in eliminating yield impacting macro defects from product wafers, as well as examples of captured defects that have identified several process tool problems are also presented. Majority of rework contributors are defects generated from intermittent photo process tool issues that randomly occur and disappear (versus systematic process tool issues that typically end up being flagged within two consecutive failed lots). Typically 0.5 to 1% of the ADI inspected wafers get reworked for macro defectivity translating to a significant number of wafers - thus justifying ADI return-on- investment. Note that real fails as a result of defectivity propagation from prior photolevels - estimated at 15% of the fail rate, do not get reworked. Additionally, real fails determined to be non-reworkable as a result of defectivity from the current photolevel - estimated at 50% of the fail rate, also do not get reworked. Further, by analyzing real fails for intra/inter wafer signatures systematic process tool issues are being consistently flagged on the line. Overall, ADI at IBM's 300mm wafer fab has evolved into a real-time wafer level go/no-go control for both product and process tools.

Previously we reported delayed cell death, defined by clear-cut cell loss 60 days after a nitrite-induced hypoxic episode. The loss of cells was not apparent two weeks after the treatment, although some changes in cellular appearance were observed at that time. A similar delayed loss of neurons in the hippocampus after hypoxia induced by blood vessel occlusion has also been found. In addition, we reported that the amount of methemoglobinemia induced by the sodium nitrite can be reduced by the stress produced by handling and the injection of saline 2 or 24 h before the nitrite administration. The degree of methemoglobin formed is directly related to cell death in certain areas of the brain, including regions within the hippocampus. Considering the many effects that can be produced by chronic and acute stress of several kinds and the length of time during which these effects manifest themselves, we undertook to determine the histologic effects of the stresses of transport on the neuroanatomic effects of sodium nitrite administration 60 days post administration. Comparisons were made of the effects of two methods of transport from the laboratory in which the animals (male CD-1 mice) were injected with the sodium nitrite or saline (Tufts Medical School) to the laboratory in which the histologic evaluations were made (Binghamton University). The animals began their travel several hours after the injections. One transport method was by commuter airline and the other was by automobile. All animals had the same transport from the supplier to the Boston location (truck). Thus, the stress of experimental interest occurred after the nitrite administration. Upon arrival at Binghamton University, the animals were housed at the University in their own colony room for 60 days before sacrifice. After sacrifice, sections from their brains were subjected to a number of histologic staining procedures, including PTAH, the Bielschowsky silver method, GFAP, and the standard Nissl procedure. Although special attention was paid to hippocampal areas, changes in cells in the habenulae and the linings of ventricular areas were also prominent. Surprisingly, the nitrite treatment before transport to Binghamton offered partial protection against the very substantial and lasting effects of the injections, transport, and handling found in the control animals. Differential effects caused by the two methods of transport were also noted.

The monoethylcholine aziridinium ion, AF64A, (3 nmol in 1 microliter) or artificial CSF (1 microliter) was infused unilaterally into the right dorsal lateral ventricle of male adult rats. Treatment with the L-type calcium channel antagonist, nimodipine (70 micrograms/kg b.wt.) or its vehicle was administered beginning before and for seven days following surgery. The infusion of AF64A reduced spontaneous alternation rates in the T-maze when compared to CSF and sham infused animals. AF64A-treated animals also took longer to reach the goal area in a complex maze task on specific trials relative to CSF and sham-infused animals. Locomotion and habituation to the open field did not differ between surgery groups. Unilateral AF64A significantly depleted acetylcholinesterase (AChE) positive terminals in the ipsilateral hippocampus and cell bodies in the ipsilateral medial septal area (MSA). Receptors for nerve growth factor (NGF-R), often colocalized with cholinergic cell bodies and terminals, also were depleted in the ipsilateral MSA of AF64A infused animals. Treatment with nimodipine did not have a neuroprotective effect on AF64A animals in either behavioral or histological results. However, some degree of protection was found in the vehicle-treated rats. This effect was likely a consequence of the stress of the injection procedure rather than the content of the vehicle, largely polyethylene glycol 400. Nimodipine-treated animals, regardless of surgery group, exhibited fewer emotional responses and had lower spontaneous alternation rates than untreated animals. The behavioral alterations found in the nimodipine groups are most easily explained in terms of altered emotionality. Overall our findings indicate that AF64A is a potent cholinotoxin that can selectively eliminate the ipsilateral septohippocampal cholinergic system when unilaterally infused into the lateral ventricle. It is possible that the mechanism of action of AF64A, like other nitrogen mustard analogues, involves disruption of basic processes involved in protein synthesis and DNA activities. Because of this, the toxic effects of the aziridinium mustard are independent of extracellular calcium and thus may not be susceptible to protection by calcium channel antagonists.

The effects of a 4-day nimodipine treatment (70 μg/kg IP beginning on the day of surgery) given to rats with lesions directed at the medial septal area were monitored for 120 days. Body weight, water intake, open-field activity, rearing, hole-poking, and repetitive motor acts were periodically measured through 120 postsurgical days. Although no differences were found in water intake between any of the groups, the body weights of rats with any medial septal damage, whether treated with nimodipine or not, were lower than rats with control operations by postsurgery day 120. Rats with any medial septal damage, whether treated with nimodipine or not, had lower rearing frequencies, rearing durations, and holepoking frequencies than controls on all test days. However, rats with complete medial septal lesions treated with nimodipine exhibited movement in the open field and frequencies of stereotyped, species-typical acts similar to those of control rats by postsurgery day 60. This nimodipine effect was not observed in rats with partial lesions of the medial septal region. This study emphasizes that a brief administration of nimodipine shortly after brain damage can influence behavioral changes 40–60 days after surgery, but that this effect was not apparent in rats with only partial medial lesions.

Animals with anterior or posterior neocortical lesions as well as intact control animals were evaluated for changes in α-adrenergic sensitivity at five postoperative times. Colonic temperature decreases were measured in response to clonidine at each of the postoperative periods. The result indicated that a heightened heat-loss response was induced by clonidine that lasted 21 or more days after destruction of the posterior neocortex. This exaggerated response to the drug was not found in animals with anterior neocortical lesions.

Offspring from pregnant rats injected with 4mg/kg body weight colchicine on Embryonic Days 18, 19, and 20 were found to have isocortical and hippocampal structures greatly reduced in mass when examined at birth. Cells with pyknotic nuclei were found in Layers 5, 4, and 3 of the cerebral isocortex, the habenula, and anterior medial nuclei of the thalamus. Brains taken at Postnatal Days 22 and 132 were reduced in overall size, and had a 20-30% reduction of cells at the vertex of the neocortex with up to 50% reduction in the thickness of the corpus callosum. A decrease in activity, an increase in fearfulness and/or decreased tendency to explore, reduced error scores on the Hebb-Williams maze, poor performance on the Maier elevated maze, and a lessened sensitivity to sound-induced seizures were correlated with these anatomical changes.

Rats with cannulas implanted into either the nucleus accumbens or the interventricular foramen were handled or handled and injected with 0, 20, 50, 80, or 1,000 ng of ACTH1–24 and then were observed for 1 h afterwards in small testing chambers. Excessive grooming was displayed in animals that had received 80 and 1,000 ng into the nucleus accumbens, but only the 1,000-ng dose was effective in eliciting excessive grooming in animals with intraventricular injections. The excessive grooming found after the 80-ng dose of ACTH in the nucleus accumbens was similar in amount and time course to that observed when 1,000 ng was injected into the ventricular system. The results indicate that the nucleus accumbens is an effective site for ACTH1–24 as it relates to excessive grooming.

Rats were prepared with radio frequency lesions of the dorsolateral or ventromedial regions of the substantia nigra. Other rats were prepared as operated and unoperated controls for each type of lesion. Their behavior was evaluated in an open field at postoperative days 2, 7, 10, and 15. Three types of behavorial changes were observed over time: those noticeable for a brief period, i.e., a few days, after the lesion (rotational behavior), those lasting 7–10 days after the lesion (turning preferences) and those lasting through the end of the experiment that may be permanent (enhanced locomotion). The early effect of the medioventral lesions was pronounced contralateral rotation while the early effect of the dorsolateral lesion was ipsilateral rotation. This effect of the dorsal lateral lesions was reversed on test days 7 and 10. Lesion-induced turning changes associated with forward locomotion were observed on these two test days as well. By 15 days after surgery the only demonstrable effect of either lesion was enhanced locomotion. The results are discussed in terms of various theories of substantia nigra regulation of motor activities.

Four experiments were undertaken to investigate the specificity of kainate-induced wet-dog shakes (WDS) to glutamate and morphine sensitive brain systems. It was shown that intraventricular (icv) administration was much more effective than intracisternal (ic) administration of kainate in producing WDS. This difference was shown not to be due to etherization of the animals during intracisternal injections. Also, like endorphin-induced WDS, kainate-induced WDS were blocked by naloxone. Kainate-induced WDS were substantially reduced by the glutamate receptor blocking agent GDEE. In a study of the relationship between morphine and kainate, behaviors induced by a low dose of morphine (such as grooming and darting movements) were blocked by subsequent administration of kainate. However, kainate-induced WDS were not affected by the morphine treatment.

The induction of excessive grooming by intraventricular administration of ACTH 1–24 was studied in rats with lesions in midbrain-limbic structures. Such areas have been reported to be implicated in mediating ACTH-induced effects on avoidance behavior, sexual excitement or stretching and yawning. Electrolytic lesions in the septal complex, the anterior hypothalamic/preoptic area, the mammillary bodies, the amygdala, the posterior thalamus and dorsal or ventral hippocampus did not interfere with ACTH-induced excessive grooming. Lesioning of the hippocampal complex by aspiration led to an inhibition of excessive grooming depending on the degree of hippocampal damage. Amygdala and hippocampal lesions enhanced the display of stretching and yawning activity after treatment with the peptide. The data indicate differences in the neural substrates mediating the effect of ACTH on extinction of conditioned avoidance behavior, excessive grooming, sexual excitement and stretching and yawning.

Rats were given sham, cortical, or hippocampal lesions and sacrificed 7 or 28 days following surgery. Levels of norepinephrine, dopamine, and the major dopamine metabolites, 3, 4-dihydroxyphenylacetic acid and homovanillic acid (HVA), were assayed in 3 brain regions. At day 7 there was a decrease in dopamine utilization and a decrease in norepinephrine levels in the nucleus accumbens after hippocampal damage but both of these measures returned to normal levels by day 28. In the neostriatum HVA levels decreased at day 7 after hippocampal damage. The utilization of dopamine in the neostriatum was decreased at day 28 in animals that received neocortical lesions but this was not observed in animals with hippocampal destruction. No effects of any lesion at any day were found in the olfactory tubercle region, the third brain region analyzed. It is thought that the removal of hippocampal and neocortical input to the basal ganglia influences catecholamine function reflected in the loss and subsequent recovery of dopamine utilization.

The effects of a 5-day ganglioside (GM1) treatment (30 mg/kg) on body weight and water intake subsequent to medial septal lesions were evaluated for 44 consecutive days. In addition, activity, rearing, and repetitive motor acts were measured on postsurgery days 5, 10, 40, and 60. The rate of increase in the body weights of rats with medial septals lesions treated with GM1 was equivalent to that of controls, while untreated rats with such lesions had reduced body weights. Rats with medial septal lesions treated with GM1 also exhibited movement times and frequency of repetitious motor acts similar to those control rats by postsurgery day 60. No differences were found in water intake between any of the groups. Rats with medial septal lesions, whether treated with GM1 or not, had equivalent frequencies of rearings that were lower than control rats. This study emphasizes that even brief regimes of GM1 administration can exert behavioral changes in brain-damaged rats well after the treatment was administered, i.e. 40–60 days after surgery.

An inexpensive input/output transfer system between a PDP-8/I Digital Equipment Corporation computer and two operant stations is described. An interrupt facility is included. Slight modification of this interface will also permit it to work with the newer PDP-8 series computers.

After immersion in water or after intraventricular administration of ACTH1–24, rats display excessive grooming behavior which in both instances can be suppressed by systemic administration of the opiate antagonist naloxone (1 mg/kg ip). If paper is glued to the walls of the observation cages, in addition to excessive grooming, water immersion or peptide administration induces paper-shredding behavior which can also be blocked by naloxone treatment. Opiate receptors seem to be involved in the mediation of both behavioral responses to water immersion. There is no relationship between scores for grooming and paper-shredding behavior. The paper-shredding behavior may be related to the piling of wood shavings often described as part of the nest-building behavior repertoire. The water immersion technique is a powerful environmental manipulation to induce grooming and may shed further light on the mechanism underlying novelty or peptide-induced excessive grooming in the rat.

Water-deprived rats were trained to approach one of four tables in an elevated X-maze for water reward. Before the first trial of each daily session, the experimenter provided information about the location of water by placing the rat on the table that was correct for that day. A correction procedure was used. The same animals served as subjects in two experiments in which either three trials (Experiment I) or seven trials (Experiment II) were given each day. In Experiment I all subjects were tested without injections, and 1 h after injection of saline or 20-, 50-, or 75-µg doses of ACTH4−10. In Experiment II subjects were tested 1 h after injection of 75 µg of ACTH4−10 on 3 days, and 1 h after injection of saline on the 3 previous days and the 3 following days. In both experiments the percentage of correct responses on the first trial was greater after 75 µg of ACTH4−10. Performance on subsequent trials was not affected. The improvement could reflect a better use of the information provided prior to the first trial or a reduced tendency to visit the table that had been correct on the previous day.

The propagation of both single epileptiform spike discharges and extended after-discharges (ADs) induced by penicillin was studied in rabbits with sections made through the caudal mesencephalon at either the midcollicular-prepontine or midcollicular-postpontine level, as well as in intact animals. Penicillin was placed either on the frontal cortex, the occipital cortex or in the dorsal hippocampus. When compared to intact controls, sectioning at the midcollicular-prepontine level increased the time required for the spike discharges to develop in the primary focus in all placements and decreased the frequency of single spike discharges when penicillin was placed in the hippocampus or frontal cortex. A transection at this level increased the duration of ADs in animals with occipital foci and made the duration of ADs originating from the frontal cortex more variable. Sectioning at the midcollicular-postpontine level decreased time required for the appearance of the spike discharges in the primary focus in subjects with occipital foci, decreased the amplitude of spike discharges in subjects with occipital or hippocampal foci, decreased duration of ADs in animals with either frontal or occipital foci, but increased duration of ADs in animals with hippocampal foci. Sections at either the pre- or postpontine level decreased the percentage of secondary ADs which continued to discharge after the AD in the primary focus had stopped. These data are taken to indicate that: (1) different mechanisms underly the development of the single spike discharge and the elaboration of these discharges into an extended AD; (2) the duration of the ADs is influenced by the ongoing background electrical activity of the brain structures involved in the AD; (3) it is likely that the same pontine and medullary structures which regulate normal synchronous electrical activity of the forebrain can also influence the hypersynchronous oscillations of the AD; and (4) an intact brain-stem may be necessary for the formation of independent secondary epileptogenic foci.

SUMMARY The establishment of secondary epileptogenic foci through the direct application of penicillin to neocortex was studied in intact rats and in ones in which the corpus callosum was sectioned either before or after the penicillin application. Section of the corpus callosum before the creation of the focus prevented the ocurrence of a region of secondary (mirror) discharge, but low voltage, long latency activity could be observed in the contralateral hemisphere which was associated with each spike discharge in the primary hemisphere. Section of the corpus callosum after the bilateral application of penicillin temporarily disrupted the synchrony of spike discharges in the 2 hemispheres. The fact that synchrony of the epileptiform discharges did return was interpreted as indicating the presence of a subcortical mechanism independent of the callosal fibers. RESUME On a etudie les modalites ďinstallation de foyers epileptiques secondaires dus aľ application directe de penicilline sur le neocortex chez des rats intacts et chez des rats auxquels on avait sectione le corps calleux soit avant, soit apres ľ application de penicilline. La section du corps calleux avant la creation du foyer prevenait ľľapparition ďun foyer en miroir, mais une decharge de bas voltage avec une longue latence, pouvait etre observee sur ľlhemisphere contralateral, en relation avec chaque decharge de pointes sur ľ hemisphere ouľon avait applique la penicilline. La section du corps calleux apres ľ application bilaterale de penicilline n'inter-rompait que temporairement la synchronic des decharges dans les deux hemispheres. La reapparition de la synchronic des decharges epileptiques apres section du corps calleux suggere ľ existence de mecanismes sous-corticaux responsables de la synchronisation independants des fibres callosales.

Rats with bilateral hippocampal damage, neocortical lesions, or sham operations were tested for excessive grooming after intracerebroventricular (icv) injection of ACTH1-24 or saline. The animals were tested for 3 days after pretreatment with low doses of haloperidol and on the first and last test days after saline pretreatment. The animals with hippocampal lesions evidenced less grooming than did the other groups, after both icv ACTH and icv saline. In addition, their grooming was reduced to a greater extent by low doses of haloperidol than was grooming by controls. This was interpreted to reflect altered dopaminergic sensitivity after hippocampal destruction.

Adult rats were given lead (0.27% Pb) in their drinking water and compared with pair-fed controls on several behavior problems: spontaneous alternation and two learning problems with three reversals of each. The lead-treated animals had reduced rates of spontaneous alternation and difficulty in changing behavior when the cues signaling reward and nonreward were reversed. In addition, animals without much handling showed exaggerated responsiveness. These changes are similar, but less extreme, than those seen in neonates treated with lead. The development of a peripheral absorption barrier may account for the reduced sensitivity of adults to lead poisoning relative to similar poisoning with younger subjects.

Rats with sham, cortical, and hippocampal lesions were trained in one-way and two-way avoidance tasks while under the influence of scopolamine hydrobromide. The performance of the hippocampal-lesion group was worse than that of the sham-operate group on the one-way task but better on the two-way task. This demonstrates the efficiency of the lesion on drugged animals, despite the similarity of effects of both the lesions and the drug injections.

Six rats with bilateral ablation of the hippocampus and six rats with extensive destruction of the neocortex were trained to enter a small compartment, while hungry, for a food reward. After 35 trials, spread over 4 days of training, the animals were given a shock while they were eating in the goal box. After the shock the rats with cortical lesions would not enter the goal compartment on the remainder of the trials given on the same day and only gradually began to re-enter over the next 2 days. The effect of the shock on the subjects with hippocampal ablation was slight and transient, suggesting that the ability to make passive avoidance responses was impaired.

Large bilateral aspiration lesions of the hippocampus in rats lead to a variety of changes in spontaneous behavior measured in an open field/hole board, relative to sham and neocortically lesioned controls. These changes include increased locomotion, and decreased grooming frequency and rearing bout duration. When animals were injected with the dopamine (DA) agonist 3,4-dihydroxyphenylamino-2-imidazoline (DPI: 0.5, 1.0 and 5.0 μg) into the nucleus accumbens one week after surgery, the behavior of hippocampally lesioned rats was restored to levels not different from control lesioned rats. Haloperidol injections (0.05, 0.1 and 0.5 μg) into the caudate nucleus were not able to do this. Further, DPI injected into the caudate nucleus one month after surgery was also able to attenuate some of the effects of hippocampal damage. On the other hand, haloperidol injections into the nucleus accumbens did not influence behavior. The results are interpreted in terms of hippocampal lesion-induced alteration of a balance in basal ganglia DA systems, indicated by modified response to pharmacological intervention and which mediate the behavioral effects of the lesion.

Adult Binghamton Heterogeneous male mice received either nimodipine (5 mg/kg in saline) or vehicle 10 minutes prior to ethanol (1.02 g/kg) administration. Blood samples were obtained at 2, 10, 30, 60 and 120 minutes following the alcohol injection for determination of ethanol content. Although mean blood alcohol concentrations (BACs) were similar for both groups, nimodipine increased the variance in blood alcohol levels. Therefore, while nimodipine may alter alcohol pharmacokinetics through its interaction(s) with the genetic characteristics of the individual animal, the ability of this calcium slow channel blocking agent to enhance the psychotropic effects of alcohol cannot be due to altered absorption or elimination of the intoxicant.

Rats were tested in a large, open field with 16 small holes in the floor. Locomotion, exploration, rearing, and grooming were measured during each 10-min testing session. When tested after injection of intraventricular saline, locomotion, exploration, and rearing were the most frequently observed behaviors. Grooming occurred only infrequently. When tested after intraventricular injection of ACTH1–24, locomotion, exploration, and rearing were greatly reduced, while grooming was markedly increased. These results indicate that the induction of excessive grooming by ACTH1–24 is not restricted to the small testing chambers usually used in such experiments and that the effect of the ACTH fragment is specific to grooming. Its effect is not an enhancement of the most prominent response being made in a particular situation.

Rats with unilateral epileptiform foci produced by daily injections of penicillin into either occipital cortex or hippocampus were trained on an operant visual discrimination. Both of the experimental groups were retarded in the acquisition of the discrimination, but the rats with foci in the occipital cortex demonstrated a more severe impairment, despite the fact that secondary epileptiform discharges appeared in hippocampus and visual cortex under both conditions. As a control for the nonepileptiform properties of the penicillin, other groups of rats received intracranial injections of sodium sulfadiazine. Rats injected with this drug were not significantly different from normal controls in the percentage of correct responses emitted, despite reduced response rates. After 5–7 days of treatment this drug produced some slight seizure activity which was unrelated to performance. On Day 11 of discrimination training the rats receiving penicillin were injected with sodium sulfadiazine and the rats receiving sodium sulfadiazine were given penicillin. The rats changed from penicillin to sodium sulfadiazine showed an immediate increase in the percentage of correct responses. Rats switched from sodium sulfadiazine to penicillin demonstrated a transitory impairment in performance. These data were interpreted to indicate that epileptiform activity produced by penicillin results in a deficit in retrieval of recently formed memories.

The actions and interactions of dihydropyridines (DHPs) and ethanol on sinus node (SN) automaticity were studied using rat sinoatrial preparations superfused with Tyrode's solution at 37 degrees C. Intracellular microelectrodes were used to monitor SN rate (SNR). The automaticity of the SN was not affected by nimodipine 10(-10) M, but it was depressed by a higher concentration of this calcium antagonist (10(-8) M). The racemic compound (+/-)Bay K 8644 had a dose-dependent biphasic chronotropic action: At 10(-8) M it decreased the SNR, while at 10(-7) M it increased the SNR. The negative component was blocked by atropine. A small concentration of ethanol (1.8 x 10(-2) M) had a positive chronotropic effect on the SN, and this action was blocked by nimodipine 10(-10) M. This small concentration of ethanol did not modify the chronotropic effects of either of the DHPs. A higher concentration of ethanol (5.3 x 10(-2) M) did not by itself affect the SNR, but it antagonized the chronotropic actions of the two DHPs.

Food-deprived rats were trained to barpress for a food reinforcement on a FR 6 schedule. After training, some received bilateral hippocampal lesions, some received bilateral cortical lesions, and some remained intact. Following postoperative recovery all rats were again food deprived and returned to the FR 6 schedule. Four doses of dl -amphetamine (0.1, 0.5, 1.0, and 1.5 mg/kg) were given, in ascending and descending orders with 1 week between each drug administration. Intact controls and controls with cortical damage demonstrated decreased response rates after the 1.0- and 1.5-mg/kg doses, whereas the hippocampectomized rats were much less affected. These results indicate that hippocampal destruction may cause a reduced reaction to amphetamine under the procedures used in this study, but it is suggested that the effect of the hippocampal lesion on amphetamine-induced behaviors may be predicted from the effect of the drug on the behavior of intact animals.

The administration of doses of ACTH 4–10 that have been shown to be effective in producing enhanced peripheral nerve regeneration did not produce the enhanced rate of decline in hyperemotionality produced by administration of the ACTH 4–9 variant Org 2766. Long-term changes in septal reactions in training situations were likewise not affected by ACTH 4–10 . These results indicate that, despite similar peripheral nerve growth effects, these two ACTH-related agents (ACTH 4–10 and Org 2766) produce quite different long- and short-term effects on rats with septal area damage.

Long-sleep (LS) and short-sleep (SS) mice were pretreated with either propranolol or phentolamine, followed by a hypnotic dose of ethanol. Pretreatment with propranolol, but not phentolamine, significantly reduced ethanol sleep time in LS mice. The SS mice were not affected. In a second study propranolol pretreatment was given subsequent to ethanol at various doses, different for each line, that produced similar sleep time durations in both lines. Under these conditions, propranolol decreased sleep time in both LS and SS mice. These data lend support to the idea that noradrenergic mechanisms play a role in the mediation of the hypnotic effects of ethanol.

Rats with unilateral lesions of either the supracallosal regions (including the dorsal cingulate cortex) and the fimbria-fornix either on the same (S) or the opposite (O) sides of the brain were studied in a 16-hole open field without pharmacologic intervention and, subsequently, after 0.1 and after 1.0 mg/kg scopolamine HBr. Their performances were compared with those of unoperated control animals subjected to the same testing regime. Certain of their behaviors were compared with those of a larger number of animals with bilateral hippocampal destruction (and their control groups) from prior studies. Unilateral lesions of fimbria-fornix and supracallosal afferents to the hippocampal formation produced a decrease in hole poking activity relative to control animals. A further decrease in hole-poking behavior, coupled with increased locomotion, was observed in rats with fimbria-fornix and cingulate cortex lesions on opposite sides of the brain (group O). The smaller dose of scopolamine accentuated these effects. Indeed, the behavior of group O after scopolamine treatment was similar to animals with large bilateral hippocampal lesions. The large dose of scopolamine induced stereotyped rearing or hole poking in the brain-damaged animals but not in the control group. These findings suggest that both the fimbria-fornix and the supracallosal pathway is necessary for normal hippocampal function and that the behavioral deficit is greater when these structures are damaged on the opposite sides of the brain.

Rats implanted with cannulas in the intraventricular foramen were tested after repeated daily injections of ACTH 1–24 or saline. Animals were either observed in their home cages or transported to an experimental room and observed in a “novel” Plexiglas chamber. Animals treated with the ACTH peptide evidenced an excessive, natural-type grooming which did not differ in the two experimental situations. No sign of adaptation of the ACTH-induced grooming was found over 10 consecutive days of testing. Saline-treated animals evidenced more grooming in the novel experimental chambers than when observed in their home cages. Some suggestion of adaptation of the grooming response was found in the saline-treated animals tested in the novel chambers. The results suggest that ACTH 1–24 induces a specific grooming response that is not dependent on being tested in a novel environment.