Medial dorsal thalamic lesions and working memory in the rat

Pigmented rats of the DA strain with either radiofrequency or ibotenic acid lesions of the thalamic nucleus medialis dorsalis were postoperatively given nonspatial and spatial tests of working memory. In the nonspatial task, delayed nonmatching-to-sample, rats with both types of thalamic lesions showed acquisition impairments. The subgroup of rats with nucleus medialis dorsalis lesions that were able to reach the acquisition criterion did, however, perform normally when the retention interval was extended to 60 s. In the spatial task, delayed forced-alternation, rats were tested with differing retention intervals and with both spaced and massed trials. Damage to nucleus medialis dorsalis had no effect on acquisition or on spaced trials, but a slight deficit was found in the animals with radiofrequency lesions under the massed trial condition. Much clearer deficits were, however, present in those animals in which the lesion extended appreciably into the anterior thalamic nuclei. The findings indicate that while cellular damage to nucleus medialis dorsalis may disrupt learning, some impairments in tests of spatial working memory attributed to this nucleus may reflect damage to the adjacent anterior thalamic nuclei.     

Effects of physostigmine and d-amphetamine on the behavior of rats with selective fimbria-fornix lesions and intrahippocampal fetal septal cell transplants

Female Long-Evans rats were given electrolytic lesions of either the medial fimbria bilaterally (Fi, n = 24), the dorsal fornix (Fo, n = 24), or both structures (FF, n = 24) at 31 days of age. Ten rats were given sham-operations. Ten days later, half the rats with lesions received bilateral intrahippocampal grafts of embryonic septal cell suspensions (FiT, FoT, FFT, respectively). As already reported in a separate publication (J.C. Dalrymple-Alford, C.R. Kelche, J.C. Cassel, G. Toniolo, V. Pallage, & B.E. Will, 1987, Experimental Brain Research, 210, 115-128), 7 months after transplant surgery, grafted rats were found to be more impaired in an eight-arm radial maze than nongrafted rats. The present report concerns a pharmacological study carried out in the same rats 11 months after grafting. We examined the effects of ip injections of physostigmine (0.01, 0.05, 0.10 mg/kg) and then of d-amphetamine (1.6 mg/kg), as compared with baseline control injections of saline. Just prior to the drug treatments, performances of grafted and nongrafted rats did not differ significantly, but impairments in grafted rats reappeared during subsequent no-injection and saline control trials. Physostigmine failed to affect significantly the performances in rats of any group. d-Amphetamine improved performances in grafted rats with medial fimbria lesions, impaired performances in grafted rats with dorsal fornix lesions, and did not change performances in grafted rats with both lesions, as compared with their respective nongrafted counterparts. Histological analysis revealed variable reinnervation of the host structure and substantial graft-induced lesions of the hippocampus.(ABSTRACT TRUNCATED AT 250 WORDS)     

Induction produced by upcoming food-pellet reinforcement: Effects on subsequent operant responding

Research has demonstrated that rats' rates of operant behavior maintained by 1% sucrose reinforcement in the first half of an experimental session are heightened when food-pellet reinforcers, rather than 1% sucrose, will be available in the second half. Experiment 1 showed that rats that had been displaying this positive induction effect acquired a new response more quickly when 1% sucrose was used to reinforce the novel response than did rats that had not been displaying induction. Experiment 2 showed that this enhanced acquisition remained even when the new response was learned in a new environment. Experiment 3 showed that unconditioned rates of making a new response did not differ between subjects that had or had not been displaying induction. Experiment 4 further showed that significantly different rates of responding on a novel task were not observed when that response was reinforced with a new, non-sucrose reinforcer. Together, the present results suggest that induction results in and/or from an increase in the reinforcing value of the 1% sucrose. As such, the present results have both theoretical and practical implications.     

Ingestive behavior in rat pups is modified by maternal sodium depletion

Developmental programming by maternal stress during pregnancy is found to influence behavioral development in the offspring. The main objective of this study was to investigate the effect of maternal sodium depletion in rats during pregnancy on the development of thirst mechanisms in the offspring. Pregnant rats underwent 3 episodes of saline depletion, induced by injecting sc 10 mg of Furosemide in saline (0.5 ml). The treatment, given on the 14th, 17th and 20th days post-conception, is thought to induce acute sodium depletion on dams. The offspring were tested for their drinking responses to Isoproterenol (500 μg/kg sc). In accordance to the known sequence of ontogenic development of drinking mechanisms, all groups of pups drunk after being stimulated with Isoproterenol at 6 days of age. The offspring from Furosemide-treated dams drank significantly less than the control group after Isoproterenol (p<0.001). Nevertheless, basal intake (water drunk after vehicle-saline only) was also significantly lower in these pups (p<0.001). In conclusion, offspring exposed to saline depletion in utero, modify their thirst responses at 6 day of age. This confirms that in utero conditions determine thirst responses in the offspring and they could provide adaptive advantages.     

Drinking and cholinergic mechanisms in the abstinence after chronic barbital treatments

Male rats were treated with barbital in the drinking water for 32–33 weeks (intake 195 mg/kg/day). This treatment ended on day 0. On days 23–29, 1.5 mg/kg/day of atropine was given. The changes induced by the treatments alone or combined were recorded either as a sensitivity to hexobarbital in the brain determined with a threshold method or as water intake calculated on data obtained with weekly intervals. The hexobarbital threshold test indicated that the barbital treatment had induced a tolerance which at the time of the atropine treatment was variable. In the rats also given the atropine treatment this tolerance was after a delay of approx. 2 weeks more marked and less variable. The water intake in only barbital treated rats showed, compared with untreated controls, an increase which had a maximum on days 28–35. During the atropine treatment given on days 23–29 there was in the previously barbital treated rats no certain effect, but immediately after the end of treatment there was an approx. 25 per cent increase in water intake above that found in only barbital treated rats. No return to control levels was seen within a 14 weeks observation period. This increase resembled supersensitivity but did not correspond over time with the changes seen in hexobarbital sensitivity.     

Aldactazide-induced consummatory and operant responding to sodium by rats.

The effects of intraperitoneal injections of Aldactazide-A on rats' consumption of water and saline solution (.51M NaCl) were tested in two experiments. During the treatment sessions, the rats showed a substantial increase in saline consumption and in lever pressing to a cue light to obtain the saline, as compared with their negligible intake before the injections and after the injections had been discontinued. The results indicate that both the drinkometer and operantbox measures are sensitive to the natroexigenic effects of Aldactazide.     

Anterior but not intralaminar thalamic nuclei support allocentric spatial memory

Medial thalamic damage is a common cause of severe memory disruption in humans. Both the anterior thalamic nuclei (ATN) and the intralaminar thalamic nuclei (ILN) have been suggested as primary sites of diencephalic injury underlying learning and memory deficits, but their respective roles have yet to be resolved. The present study explicitly compared two spatial memory tasks in male PVGc hooded rats with selective neurotoxic lesions to either (1) the ATN or (2) the rostral ILN (and adjacent lateral mediodorsal thalamic nuclei; ILN/LT lesions). As predicted, the ATN group, but not the ILN/LT group, exhibited clear deficits in the Morris water maze task for the initial acquisition of a fixed hidden platform and its reversal to a new position. The second task examined acquisition of egocentric spatial reference memory for a left or right body turn, using any three arms in an 8-arm water maze on any given trial; contrary to predictions, both lesion groups performed as well as the Sham group. The lack of deficits in ILN/LT rats on this second task contrasted with previous findings reporting a detrimental effect of ILN/LT lesions on egocentric working memory. The clear dissociation between the influence of ATN and ILN/LT lesions with respect to allocentric spatial reference memory in the Morris maze emphasizes that caution is required when interpreting the effects of non-ATN thalamic lesions on spatial memory when the lesions encroach substantial areas of the adjacent ATN region.     

The role of hyperdipsia in aggression following septal lesions in rats

Lesions of the septum in animal subjects are known to produce an increase in aggressiveness and an increase in water intake. A series of experiments was carried out to examine the possibility that aggression was secondary to hyperdipsia. When rats with septal lesions were restricted to preoperative levels of water intake, aggression scores declined significantly. When animals without lesions were preloaded, with either water or saline, aggression increased. Neither decreased shock threshold nor increased cell hydration provided a full explanation for the results. It is suggested that the aversive nature of the stomach turgescence caused by increased water intake may be an additional mediating factor in septal aggression.     

Effects of progesterone and nesting materials on response prevention and extinction of avoidance in rats

Female rats received either progesterone or saline injections prior to learning a simple one-way avoidance response. During a 10-min response prevention procedure half of the animals in each group had nesting material present while the remaining rats did not. The availability of nesting material during response prevention hastened extinction while progesterone injections significantly increased the frequency of nesting activities during response prevention but did not affect rate of extinction. The availability of nesting materials increased the frequency of standing but reduced the frequency of crouching. The results were discussed in terms of the role of ethological displacement activities during response prevention as well as the role of ‘relaxational’ activities as discussed by Baum and Denny.     

Interactive effects of deprivation in the albino rat

The interactive effects of feeding and drinking schedules were investigated in three experiments. Twenty-four hour water-deprived rats consumed their entire obligatory water intake prior to feeding, whereas 24-hr food-deprived rats consumed only small quantities of food prior to drinking. This drinking was apparently due to a shift of water stores rather than an actual negative water balance. Experiment 3 investigated the effects of 24, 48, or 72 hr of water, food, or total deprivation. Water-deprived rats did not adequately suppress food intake and became thirstier than totally deprived rats. The effects of total deprivation were essentially identical to those of food deprivation. These experiments indicate the degree to which deprivation schedules impose restrictions on the reinforcement parameters of behavioral experiments.     

The effects of chronic water deprivation on metabolic rate and long-trace taste-aversion conditioning in rats

The effect of chronic water deprivation on metabolic rate and long-trace taste-aversion conditioning was examined in Wistar-derived rats. Subjects were either maintained on a water deprivation regimen or allowed free access to water for a seven-week period prior to conditioning. At conditioning, rats were presented a saccharin CS followed 0-, 45-, 90-, or 180-min later by an i.p. injection of LiCl. Additionally, pseudo-conditioned groups were presented the CS followed immediately by an injection of physiological saline. Heightened oxygen consumption in deprived subjects suggested that chronic water deprivation increased metabolic rate. While no differences in the amount of saccharin intake were observed at conditioning, percent preference for saccharin scores during a 24-h two-bottle water/saccharin test revealed that non-chronically deprived rats supported conditioning at longer CS-US intervals than did chronically water-deprived rats. Results are interpreted in terms of a time-contraction effect stemming from an alteration of an internal metabolic count-down timer.     

The effect of acceleration on food-reinforced DRL and FR

Performance on DRL 10 sec and FR 5 was studied after exposure to acceleration. After four rats, two on each of the above schedules, had stabilized they were exposed to 5 hr of acceleration at 5 G immediately before daily experimental sessions. Food intake was also studied in rats given access to food daily in their home cages and exposed to acceleration immediately before the free-feeding session. Weight gain of free-feeding animals and reinforcement intake of experimental animals dropped after acceleration. Over-all response rate on the FR was depressed markedly by acceleration but local response rates did not appear to be affected. IRT distributions of DRL sessions after acceleration were markedly shifted toward the long intervals. A sequential plot of IRTs on acceleration days showed an altered, but relatively stable, temporal patterning of responses followed by an abrupt return to the normal baseline toward the end of the session.     

Medial septal lesions: disruptions of microregulatory patterns and circadian rhythmicity in rats

The microregulatory patterns of food and water intake were examined in male and female rats bearing medical septal lesions and in sham-operated controls. Medial septal ablation, although not affecting the total amount of food or water ingested, resulted in a profound disruption of the pattern of intake. Circadian rhythmicity was disrupted for a period, returning to normal by 25 days postlesion. Permanent disruptions occurred in feeding patterns in the rats with septal lesions ingested more frequent but smaller meals. There was also a marked increase in food-intake-associated drinking and a decrease in non-food-intake-associated drinking. The results are interpreted to reflect two separate independent effects, a general circadian disruption and an alteration in requlatory behavior produced by a chronic depletion of body fluid.     

Preoperative enrichment and behavioral recovery in rats with septal lesions

To assess the behavioral effects of preoperative differential housing male rats were placed in either enriched or isolated environments at weaning prior to receiving either sham operations or septal lesions when 57 days of age. Rats with septal lesions showed reduced habituation of ambulation and initially made fewer rears in an empty open field but made more object-contacts coupled with a lack of habituation in the object-filled field. Septal rats also showed severe impairments when tested in a 12-arm radial maze with 7 arms baited and 5 arms unbaited. Preoperative enrichment did not significantly affect these lesion-induced changes. Nevertheless, enrichment significantly lowered ambulation (but did not affect habituation) in the open field and increased the number of manipulatory relative to nonmanipulatory contacts. However, preoperatively enriched septal rats showed a deficit in spontaneous alternation (45%) in contrast to the high levels (83%) shown by intact enriched rats, whereas both intact and septal isolated rats showed similar levels of spontaneous alternation (68%). These results conflict with earlier reports that preoperative enrichment "protects" rats against the deficits produced by septal lesions.     

The effect of hunger on water intake in rats

Although reciprocal inhibition between eating and drinking has been postulated, the commonly observed reduction of water intake by hungry rats may not be due to any direct inhibitory mechanism. In one experiment rats deprived of food for 24 hr. and then injected with 2 ml. of NaCl drank the same as rats that had received food ad lib. In the second experiment a stomach load of 10 ml. of water 3 hr. before the salt injection was designed to abolish any water deficit that might have occurred during food deprivation had there been inhibition of drinking by hunger. Here again rats deprived of food did not drink less than undeprived animals. In fact the hungry rats drank slightly but significantly more. This phenomenon may be related to the observation confirmed here that during food deprivation rats excrete about twice as much rather dilute urine as during ad lib food intake. This seems to indicate that though in general food deprived rats drink less than normal they actually drink more than they need. Schedule induced polydipsia also occurs during food deprivation and this too makes it unlikely that water-intake is actually inhibited during hunger.     

Is blockade of conditioned flavor aversions by chlorpheniramine the result of state dependency?

Conditioned flavor aversions induced by pairing flavored fluids with ionizing irradiation, lithium chloride, estrogen, or centrifugal rotation have been blocked by prior administration of chlorpheniramine. The blockade may be due to state dependency. This possibility was evaluated in the present experiment, which assigned female Long-Evans rats to a factorial combination of chlorpheniramine (20 mg/kg) vs saline during training, centrifugal rotation (150 rpm for 15 min) vs none as an UCS, and chlorpheniramine vs saline in testing. Rats conditioned with saline and rotation showed strong aversions when tested with either same or chlorpheniramine. Rats conditioned with chlorpheniramine and rotation showed no change during conditioning; when tested with saline they showed no aversion, and when tested with chlorpheniramine they showed no change from conditioning. Rats conditioned with either chlorpheniramine or saline and no rotation showed high fluid intake when tested with saline and reduced fluid intake when tested with chlorpheniramine. The results were interpreted as offering little support for state dependency.     

Amino Acid Effects on Post-Stress Ulcers: Relationship to Brain Serotonin, 5-HIAA and Norepinephrine

To replicate and extend results of earlier studies on amino acid effects on post-stress ulcers, rats were subjected to i.p. injections of (a) saline, (b) tryptophan, (c) tyrosine + valine or(d) tryptophan + tyrosine + valine, either 30 minutes before or immediately after one hour of water restraint stress. Gastric lesions, brain norepinephrine, serotonin and 5-hydroxyindoleacetic acid (5-HIAA) were examined after one hour of poststress rest. We hypothesised that post-stress lesions could be aggravated by central noradrenergic hypoactivity and serotonergic hyperactivity during the post-stress period. Other studies have indicated that tyrosine + valine reduces central serotonergic activity, while additional tryptophan blocks this effect. We therefore expected post-stress lesions to be reduced in tyrosine + valine but not in tryptophan + tyrosine + valine treated animals. Although these expectations were met tentatively in animals injected prior to stress, thus replicating tyrosine + valine effects we had observed earlier, opposite results were found in animals treated post-stress. The brain analyses indicate that the data cannot be explained by a norepinephrine/serotonin imbalance hypothesis. The time dependency of the effects underlines the need for caution in clinical applications of these amino acid treatments.     

Increased analgesia to thermal stimuli in rats after brief exposures to complex pulsed 1 microTesla magnetic fields

Nociceptive thresholds to a 55 degrees C hot surface were measured for female Wistar rats before treatments and 30 min. and 60 min. after the treatments. After injection with either naloxone or saline following baseline measurements, the rats were exposed for 30 min. to either sham fields or to weak (about 1 microTesla) burst-firing magnetic fields composed of 230 points (4 msec. per point) presented once every 3 sec. The rats that had received the burst-firing magnetic fields exhibited elevated nociceptive thresholds that explained about 50% of the variance. A second pattern, designed after the behaviour of individual thalamic neurons during nociceptive input and called the "activity rhythm magnetic field" produced only a transient analgesic effect. These results replicated previous studies and suggest that weak, extremely low frequency, pulsed magnetic fields with biorelevant temporal structures may have utility as adjuncts for treatment of pain.     

The effects of concurrent manipulations of cholinergic and noradrenergic systems on neocortical EEG and spatial learning

In the spatial learning test, young animals were divided into three groups receiving saline, scopolamine (0.15 mg/kg), or scopolamine (0.8 mg/kg). Half of the animals in each group were lesioned with DSP-4 to destroy noradrenergic fibers. DSP-4 lesions did not produce any significant impairment alone or in combination with a lower dose of scopolamine (0.15 mg/kg), but they did further augment the scopolamine (0.8 mg/kg)-induced defect. In the electroencephalography (EEG) experiment, both control rats and DSP-4-lesioned rats were recorded after receiving saline, scopolamine (0.15 mg/kg), and scopolamine (0.8 mg/kg) injections. Scopolamine induced a dose- and behavioral state-dependent EEG slowing, whereas DSP-4 lesions did not change either baseline EEG activity or EEG reactivity to scopolamine.     

Clamped Corticosterone (B) Reveals the Effect of Endogenous B on Both Facilitated Responsivity to Acute Restraint and Metabolic Responses to Chronic Stress

To determine the effects of both corticosterone (B) and chronic stressors on acute ACTH responses to restraint, young male rats were exposed to streptozotocin-induced diabetes, cold (5-7 degreesC) or intracerebroventricular (icv) neuropeptide Y (NPY) for 5 d and then exposed to restraint within 2 h after lights on. Two groups of rats were studied: intact and adrenalectomized replaced with B pellets that maintained plasma B in the normal mean 24-h range of intact rats. In addition to ACTH and B responses to restraint on d 5, body weight, food intake, fat depots, glucose and other hormones were measured to determine the role of stress-induced elevations in B on energy balance. ACTH responses to restraint were normal in intact rats subjected to diabetes or cold. By contrast, there was no ACTH or B response to restraint in NPY-infused intact rats. All 3 groups of chronically stimulated adrenalectomized rats with clamped B had facilitated ACTH responses to restraint compared to their treatment controls. Overall food intake increased in all groups of stressed rats; however, augmented intake occurred only during the light in intact rats and equally in the light and dark in B-clamped rats. White adipose depot weights were decreased by both diabetes and cold and increased by NPY in intact rats; the decreases with cold and increases with NPY were both blunted and changes in fat stores were not significant in adrenalectomized, B-clamped rats. We conclude that: 1. diabetes- and cold-induced facilitation of restraint-induced afferent input to hypothalamic control of the hypothalamo-pituitary-adrenal (HPA) axis is opposed in intact rats by the elevated feedback signal of B secretion; 2. NPY does not induce facilitation of afferent stress pathways; 3. chronic stimulation of the HPA axis induces acute hyperresponsiveness of hypothalamic neurons to restraint provided that the afferent input of this acute stimulus is not prevented by B feedback; 4. stimulus-induced elevations in B secretion result in day-time feeding; 5. insensitivity of both caloric efficiency and white fat stores to chronic stress in adrenalectomized, B-clamped rats results from loss of normally variable B levels.