Environmental stimulation and fucose incorporation into brain and liver glycoproteins

Changes were observed in the amount of radioactive fucose incorporated into glycoproteins of brain and liver when mice were exposed to different environments. Mice were injected subcutaneously with ³H-L-fucose, placed in a small chamber with an electrifiable grid floor for 15 min, and killed 1 min later. Exposure to the apparatus without shocks increased the levels of incorporation in both and liver compared to mice placed in individual cages after the injection. Increasing amounts of footshock reduced the level of incorporation. Five to 40 sec of footshock resulted in incorporation levels inversely proportional to the number of shocks.     

Uptake of 3H-uridine into brain and incorporation into brain RNA of rats exposed to various training tasks - a biochemical analysis.

Operant schedules were used to isolate component parts of a training task and rates of incorporation of 3H-uridine into the brain and brain RNA were determined. Rats that developed a discrimination in responding to a visual stimulus absorbed more radioactivity into the brain and incorporated a higher percentage of this radioactivity into total and cytoplasmic RNA than littermates exposed to the visual stimulus only. Of the component parts of the training task, the discrimination accounted for the greatest increase in absorption of radioactivity and incorporation of it into RNA. The schedule change had the second largest effect and the stimulus change the least.     

Effect of haloperidol on glutamete decarboxylase activity in discrete brain areas of the rat

Using freeze-dried samples of rat brain, the effect of haloperidol on glutamate decarboxylase (GAD) activity without exogenously added pyridoxal-5-phosphate (PLP) was studied in discrete brain nuclei and areas. Repeated injections of haloperidol produced significant changes in GAD activity in the dorsal part of the caudate nucleus, entopeduncular nucleus, pars reticulata of the substantia nigra, lateral hypothalamic area, and dorsomedial hypothalamic nucleus. A reduction of GAD activity after haloperidol was observed in the entopeduncular nucleus and pars reticulata of the substantia nigra. This finding demonstrates biochemically that haloperidol-induced extrapyramidal behavior may be involved in the reduction of GABAergic transmission in the entopeduncular nucleus and pars reticulata of the substantia nigra. A decrease in GAD activity in the lateral hypothalamic area indicates that interaction between GABAergic neurons as well as dopaminergic neurons may be involved in the haloperidol-induced behavioral changes. In addition, close interaction between GABAergic and dopaminergic systems in the dorsomedial hypothalamic nucleus and dorsal part to the caudate nucleus was demonstrated.     

Beta-endorphin causes retrograde amnesia and is released from the rat brain by various forms of training and stimulation

The endogenous opiate peptide, beta-endorphin (0.4, 1.0, 2.0, and 10.0 g/kg) was injected IP into rats immediately after training in a shuttle avoidance task, and its effect on memory retention was evaluated in test sessions carried out 24 h later. The drug was found to cause retrograde amnesia, the ED₅₀ being 1.0 g/kg. Beta-endorphin immunoreactivity was measured in the hypothalamus and rest of the brain of rats submitted to training, or test sessions of shuttle avoidance learning, pseudoconditioning in the shuttle-box, tones alone, or foot-shocks alone. After training in any of the four paradigms, there was a marked (46–60%) depletion of beta-endorphin immunoreactivity in the rest of the brain. No changes were detected in the hypothalamus or after test sessions. The loss of beta-endorphin immunoreactivity may be attributed to release of this substance caused by the stimuli used for training. From the present findings, as well as previous observations on the memory-facilitating influence of the opiate receptor antagonist, naloxone, it is concluded that there is a physiological amnesic mechanism mediated by beta-endorphin (and perhaps other opoid peptides as well), which is triggered by the non-associative factors present in the various forms of learning.Supported by funds from FAPERGS, PROPESP-UFRGS, and CNPq, Brasil     

Electrical stimulation and lesions of the medial forebrain bundle of the rat: Changes in voluntary ethanol consumption and brain aldehyde dehydrogenase activity

Repeated sessions of electrical stimulation or lesions in the ventral aspect of the medial forebrain bundle (VMFB) region of the brain in rats resulted in a significant increase and a decrease in voluntary ethanol (10% v/v) intake, respectively. Whole brain and midbrain-diencephalon (MB-DE) aldehyde dehydrogenase (ALDH) were measured in different groups of experimental and control animals before, immediately after, and 30 days after the termination of the stimulation regimen, or 8 days and 30 days after the induction of the lesions. By the end of the stimulation regimen, the levels of MB-DE ALDH of the experimental (ethanol-drinking: stimulated) animals were significantly higher than those of control animals (ethanol-drinking: nonstimulated, water-drinking: stimulated, and water-drinking: nonstimulated). A marked decrease in MB-DE ALDH activity was noted in lesioned animals but not in cyanamide-treated or in implanted control animals. Neither the stimulation nor the lesions had any demonstrable effect on whole brain ALDH activity. Cyanamide administration caused a pronounced decrease in ethanol intake and in levels of liver ALDH activity. The increase in MB-DE ALDH activity in the ethanol-drinking, stimulated animals was attributed to the interaction between the VMFB activation and the ethanol drinking, while the reduction in ALDH activity was attributed to the degeneration of biogenic-amine-containing nerve fibers.     

Glucosamine incorporation into rat cerebrum: Effect of adrenalectomy,corticosterone, exercise,and training

Incorporation of D-[l-¹⁴C]glucosamine into various metabolic fractions was studied in an experiment designed to quantify the relative influence of physiological and behavioral factors. Different physiological states were established by sham operation (S), adrenalectomy (A), and adrenalectomy plus corticosterone replacement (H). Within each physiological condition the behavioral state was varied by swim-escape training (E), swimming exercise (X) or nonswimming controls (C). Adrenalectomy caused a generalized increase in label uptake by cerebral cortex and hippocampus, but precursor levels in the blood were elevated also, suggesting a systematic physiological effect. Behavioral state had no effect on overall uptake, but did influence the distribution of label between soluble and membrane-bound glycoproteins. These results indicate that D-[l-¹⁴C]glucosamine is an effective glycoprotein and ganglioside precursor in behavioral experiments, provided corrections for the influence of systematic physiological factors are made.     

Effect of naloxone and morphine on various forms of memory in the rat: Possible role of endogenous opiate mechanisms in memory consolidation

Naloxone, morphine, and morphine plus naloxone were injected IP into rats immediately after training in several different behavioral tasks, and their effect on retention was evaluated in test sessions carried out 1 or 7 days later. Naloxone (0.4 mg/kg) enhanced and morphine (1.0 mg/kg) depressed retention for a standard shuttle avoidance task acquired with contiguous tone-footshock presentations. Retention of this behavior is known to result from the independent operation of four memory channels (Izquierdo and Elisabetsky, 1978). In consequence, the effect of naloxone on each of those channels was investigated. The channel which stores responses acquired through an avoidance mode and makes them available for retrieval in the same mode, was facilitate by as little as 0.2 mg/kg of the drug. The other channels were sensitive only to 0.4 or 0.8 mg/kg naloxone. Retention of the habituation of a rearing response to a tone from one day to the next was also enhanced by naloxone (0.8 mg/kg) and depressed by morphine (1.0 mg/kg), and, again, there was an antagonistic interaction between the two drugs. The results suggest a role for endogenous opiate substances as general inhibitory modulators of memory consolidation, point to a differential sensitivity of the various memory channels to naloxone (therefore, presumably to endogenous opiate modulation), and demonstrate that the post-training effect of naloxone and morphine on memory (or the role of endogenous opiates thus suggested) does not depend on the presence of foot shocks in the training session to become manifest.     

Comparison of acute and chronic lithium treatment on 3H-norepinephrine uptake by rat brain slices

The effects of lithium chloride, given IP in high (2.5–15 mEq/kg) and low (1.25 mEq/kg) doses twice daily, upon ³H-norepinephrine uptake and retention were examined with slices from four regions of the rat brain, namely brain stem, hypothalamus, parietal cortex, and caudate nucleus. Control uptake was significantly higher in slices from the caudate nucleus and lower in brain stem slices than in slices from hypothalamus or parietal cortex. With the higher doses, uptake increased significantly in all regions after 2 days of treatment and returned to normal by 7 days. With the lowest dose, uptake was increased after 7 days but normal at 14 days. Only in caudate slices was there a second elevation of ³H-norepinephrine uptake after 21 days of treatment, which returned to normal by 42 days. No other effects were observed during 70 days of treatment with lithium. The correlation between changes in ³H-norepinephrine uptake and plasma lithium levels was studied.     

Effects of handling and etherization on incorporation of [3H] lysine into protein of mouse brain and liver

A standardized handling experience of 20 sec duration elevated the amount of radioactive lysine incorporated into brain total proteins during a 10 min labeling period begun either 10 min or 30 min after the handling. Etherization for 20 sec produced similar metabolic changes. Incorporation of [³H] lysine into liver proteins was minimally affected by handling, while slightly altered by etherization. The metabolic changes detected in the brain after handling did not appear to be side-effects of changes in blood-borne radioactivity. The results indicate that laboratory stresses often thought to be of minor importance can have large effects on ordinary assays of protein metabolism in brain.     

Effect of beta-adrenoceptor blocking drugs on 32P incorporation into and arachidonic acid liberation from phospholipids in stimulated rat mast cells

The lipophilic beta-adrenoceptor blocking (BAB) drugs metipranolol, propranolol and exaprolol significantly decreased 48/80- and A23187-induced 32P incorporation into rat mast cell phospholipids. Exaprolol was the most active, followed by propranolol and metipranolol. Atenolol and metipranolol significantly decreased the 48/80-stimulated, and metipranolol and exaprolol the A23187-stimulated 3H-arachidonic acid liberation from isolated mast cells.     

The effects of chronic nicotine on spatial learning and bromodeoxyuridine incorporation into the dentate gyrus of the rat

Rationale Nicotine is reported to improve learning and memory in experimental animals. Improved learning and memory has also been related to increased neurogenesis in the dentate gyrus (DG) of the hippocampal formation. Surprisingly, recent studies suggest that self-administered nicotine depresses cell proliferation in the DG. Objective To test the hypothesis that the effects of nicotine on cell proliferation in the DG and learning and memory depend upon the nicotine dose administered. Methods Rats were chronically infused from subcutaneous osmotic mini pumps with nicotine (0.25 or 4 mg kg⁻¹ day⁻¹) or the saline vehicle for 10 days. Half the rats in each treatment group were trained to locate a hidden platform in a water maze task on days 4–7; a probe trial was performed on day 8. The remaining rats remained in their home cages. The effects of nicotine and of training in the water maze task on cell genesis in the DG were determined by measuring 5-bromo-2′-deoxyuridine (BrDU) uptake using fluorescence immunohistochemistry. Results Training in the water maze task increased cell proliferation in the DG. Infusions of nicotine at 4 mg kg⁻¹ day⁻¹, but not 0.25 mg kg⁻¹ day⁻¹, decreased cell proliferation in both untrained animals and animals trained in the maze and impaired spatial learning. Conclusions The data suggest that learning in the water maze task is impaired by higher doses of nicotine tested, and that this response may be related to reduced cell genesis in the DG.     

Effects of electrical stimulation of the reticular formation and chlorpromazine on performance of trace conditioned avoidance response in the rat

The effects of electrical stimulation to the mesencephalic reticular formation and chlorpromazine on the performance of a trace conditioned avoidance response by rats were studied. Either treatment alone impaired the performance; this impairment was a function of level of stimulation or dose of the drug, respectively. The performance deficit was not present when a high intensity of stimulation of the reticular formation was combined with a moderate dose of chlorpromazine. However, the combination of a high dose of the drug with a low stimulation intensity interfered with the avoidance responding more than any other condition tested. These effects appeared to be independent of neutral or negative reinforcement effects of the stimulation, as tested in an independent situation.     

Effects of chronic administration of delta 9-tetrahydrocannabinol on the cardiovascular system, and pressor and behavioral responses to brain stimulation in freely moving rats

The effects of chronic administration of delta 9-THC on the cardiovascular system, and the pressor and behavioral responses to brain stimulation were investigated in freely moving rats with chronic electrode and arterial cannula implants. delta 9-THC at a dose of 6 mg/kg was injected intraperitoneally once a day for 10 days through an abdominal cannula. On the first day, delta 9-THC induced a significant decrease in heart rate and rise in blood pressure. The animals exhibited abnormal behavior such as catalepsy, walking backward and pivoting. On the 5th day, the bradycardia induced by delta 9-THC markedly decreased and on the 10th day tachycardia was observed. The pressor effect of delta 9-THC significantly increased on the 5th and 10th days. However, delta 9-THC-induced abnormal behavior was observed without any changes following chronic administration. delta 9-THC inhibited the pressor response and behavioral changes to electrical stimulation of the posterior hypothalamus and midbrain reticular formation. No tolerance developed to these depressive effects of delta 9-THC after chronic treatment. These data suggest that tolerance develops only to bradycardic effect of delta 9-THC and that the decrease in vagal activity may play some role in the development of tolerance.     

Properties of a 125I-substance P derivative binding to synaptosomes from various brain structures and the spinal cord of the rat

Summary Using crude synaptosomal fractions (P₂ fractions) and ¹²⁵I-Bolton and Hunter substance P (¹²⁵I-BHSP) as a ligand, the characteristics of specific binding sites were examined in various brain structures and in the spinal cord (dorsal and ventral parts) of the rat. Scatchard plots revealed the occurrence of a single class of binding sites in the various structures studied with comparable K _d values (from 0.46 to 1.10 nmol/l in the brain and 0.51, 0.56 nmol/l in the spinal cord dorsal and ventral parts respectively) and of marked differences in the number of binding sites (B_max) (septum > striatum > hippocampus, hypothalamus > mesencephalon > cerebral cortex and dorsal part of the spinal cord > ventral part). In the brain no correlation was found between the number of ¹²⁵I-BHSP binding sites and the amount of substance P levels (substance P-like immunoreactivity) in synaptosomes, particularly in the hippocampus and the substantia nigra since the former structure was characterized by its low substance P content and its high number of binding sites and the reverse was observed in the substantia nigra. The ability of several C- and N-terminal fragments of substance P and of tachykinins to compete with ¹²⁵I-BHSP binding to synaptosomes from the hippocampus, the hypothalamus and the dorsal part of the spinal cord was then determined. Results obtained were closely similar from one structure to another and comparable to those previously reported using whole brain synaptosomes. Although the presence of various types of central substance P receptors cannot be excluded, the present results indicate that only one class of sites can be demonstrated using ¹²⁵I-BHSP as a ligand.Abbreviations used ¹²⁵I-BHSP ¹²⁵I-Bolton-Hunter substance P - HPLC high pressure liquid chromatography     

Comparison of the effect of prostaglandin E1 and norepinephrine injected into the brain on ingestive behavior in the rat

Norepinephrine hydrochloride (NE) in doses of either 5 or 25 μg and prostaglandin E₁ (PGE₁) in doses of either 5 or 50 ng were made directly into the substance of the hypothalamus as well as other limbic structures of the unrestrained, unanesthetized rat. The animals had free access to food and water at all times. NE injected into the perifornical area of the hypothalamus, the hippocampus and the amygdala elicited vigorous eating. PGE₁ did not produce eating which differed from that observed following control injections of a physiological control solution. Drinking was not observed following injections of either NE or PGE₁ at the dose used. These data indicate that PGE₁ does not play a direct role in the hypothalamic and limbic control of ingestive behavior.