Biomedical subjects

C Dalmaz

Publications and source records attributed to C Dalmaz.

33 records · Page 2Linked to original sources

PubMed1996

Amygdala beta-noradrenergic influences on memory storage involve cholinergic activation.

These experiments examined the involvement of the amygdaloid complex as a site of interaction of adrenergic and muscarinic cholinergic influences on memory storage. Male Sprague-Dawley rats (60 days old; 250-300 g) were given a single training trial in an inhibitory avoidance task and a retention test trial 48 h later. Immediately after training buffer control or drug solutions (0.5 microliter) were infused into the amygdala and, in the first experiment only, other drugs were administered intraperitoneally (ip). The first experiment examined the effects of post-training systemic injections of the muscarinic agonist oxotremorine (100.0 micrograms/kg) administered alone or together with intraamygdala injections of either the muscarinic antagonist atropine (1.0 microgram) or the beta-noradrenergic antagonist propranolol (0.3 microgram). Oxotremorine enhanced retention and atropine, but not propranolol, attenuated the effects of oxotremorine. In the second experiment intraamygdala infusions of the beta-noradrenergic agonist clenbuterol (10.0 ng) were administered either alone or together with atropine (1.0 microgram). Clenbuterol enhanced retention and atropine blocked the effects of clenbuterol. In the third experiment intraamygdala infusions of oxotremorine (3, 10, 30, or 100 ng) were administered either alone or together with propranolol (0.3 microgram). Oxotremorine (3.0 and 10.0 ng) enhanced retention and propranolol did not block the effects of oxotremorine. These findings are consistent with the view that memory storage is regulated by an interaction of beta-noradrenergic and cholinergic influences and suggest that the noradrenergic influences are mediated by the release of acetylcholine and activation of muscarinic cholinergic receptors within the amygdala.

Acetylcholine↗

PubMed1993

Neuromodulatory systems and memory storage: role of the amygdala.

This article reviews findings of research examining the interaction of peripheral adrenergic systems with cholinergic, opioid peptidergic and GABAergic systems in modulating memory storage. It is well established that retention is enhanced by posttraining systemic or intra-amygdala injections of adrenergic agonists, opiate antagonists and GABAergic antagonists. These influences appear to be mediated by activation of NE receptors within the amygdala, as intra-amygdala injections of beta-adrenergic antagonists block the memory-modulating effects of hormones and drugs affecting these systems. Furthermore, these influences also appear to involve, at a subsequent step, activation of a cholinergic system: atropine blocks the memory-enhancing effects of adrenergic agonists and opiate and GABAergic antagonists and oxotremorine attenuate the memory-impairing effects of opiate agonists and GABAergic agonists. These findings suggest that the amygdala integrates the memory-modulating effects of neuromodulatory systems activated by learning experiences.

Amygdala↗

PubMed1993

Noradrenergic and cholinergic interactions in the amygdala and the modulation of memory storage.

Numerous studies have reported that, in rats, memory can be affected by manipulations of the amygdala noradrenergic system. Typically, low doses of norepinephrine facilitate while higher doses impair memory storage. Muscarinic cholinergic agonists facilitate, while antagonists impair memory storage. Recent evidence from studies using systemic injection of drugs, indicates that these two systems interact in modulating memory storage. The experiments reported here examined interactions between the amygdala noradrenergic and muscarinic cholinergic systems. The results indicate that activation of muscarinic cholinergic mechanisms in the amygdala enhances retention, and that such activation mediates the facilitatory effects of systemically administered oxotremorine. beta-Noradrenergic agonists appear to exert their effects in the amygdala by activating the release of acetylcholine.

Amygdala↗

PubMed1991

Biochemical and behavioral effects of intraseptal microinjection of fasciculin, an irreversible acetylcholinesterase inhibitor.

1. We examined the effect, in rats, of an intraseptal microinjection of fasciculin (FAS), an irreversible peptide acetylcholinesterase (AChE) inhibitor, on a) AChE activity measured in septum and hippocampus, b) 3H-quinuclidinyl benzylate (3H-QNB) and 3H-oxotremorine (3H-OXO) binding to hippocampal cholinergic muscarinic receptors, c) 3H-flunitrazepam (3H-FNZ) binding to hippocampal benzodiazepine receptors as a control for QNB and OXO binding, d) acquisition and retention in three different behavioral paradigms, i.e., water-finding (in which there is concomitant habituation to the apparatus), step-down inhibitory avoidance, and shuttle avoidance. 2. AChE activity in septum decreased 2 days (-66%) and 5 days (-48%) after FAS microinjection; a slight reduction (-35%) occurred in the dorsal hippocampus on day 2 (P less than 0.05; N = 6 per group); no changes in AChE activity were observed in ventral hippocampus on day 2 or day 5. 3. No changes in 3H-QNB, 3H-OXO, or 3H-FNZ binding constants were demonstrable in the hippocampus either 2 or 5 days after intraseptal FAS administration. 4. No changes in training or test session performance in any of the three behavioral situations were observed 2-3 days after the intraseptal microinjection of FAS. 5. The persistent inhibition of septal AChE caused by FAS microinjection into the septum is not sufficient to induce major changes either in hippocampal cholinergic muscarinic receptors, or in the learning or retention of behaviors regulated by the septum and/or hippocampus.

Animals↗

PubMed1990

Bilateral injection of fasciculin into the amygdala of rats: effects on two avoidance tasks, acetylcholinesterase activity, and cholinergic muscarinic receptors.

These experiments examined the effects of the bilateral injection of fasciculin-2 (FAS), a natural acetylcholinesterase (AChE) inhibitory peptide, into the amygdala of rats on acquisition and retention of two avoidance behaviors. Intraamygdala injection of FAS (150 ng/amygdala) produced a pronounced and long-lasting inhibition of AChE activity: 85% and 74% on day 2 and day 5, respectively. After 48 hr, FAS-treated animals showed no changes in training or test session performance in a step-down inhibitory avoidance task (training-test interval was 24 hr). In a 2-way shuttle avoidance task, intraamygdala FAS slightly reduced retention test performance without modifying training session scores. Two and five days after FAS injections into the amygdala, the density of muscarinic receptor decreased about 50% as measured by the specific bindings of 3H-quinuclidinyl benzilate and 3H-oxotremorine. No alterations were observed in the apparent dissociation constants. On the other hand, the central-type benzodiazepine receptor population of the amygdala remained unchanged, suggesting that FAS microinjection did not produce damage to neuronal components of these nuclei. In conclusion, the results presented have indicated that a clear-cut and long-lasting inhibition of AChE activity in the amygdala is not accompanied by a facilitation of learning and memory of two different avoidance tasks. Compensation of the increased cholinergic activity by a down-regulation of muscarinic receptors could account for these findings.

Acetylcholinesterase↗

PubMed1989

Gamma-endorphin affects retrieval of an inhibitory avoidance task.

Rats were trained in a step-down inhibitory avoidance task and retrieval was measured during a test session conducted 24 h after training. The ip administration of a low dose of gamma-endorphin (0.2 micrograms/kg) immediately after training reduced retrieval time from 40.6 to 13.5 s (N = 15). Higher doses of gamma-endorphin given 5 min before testing (1.0 micrograms/kg) or immediately after training (5 micrograms/kg) enhanced retrieval time from 38.6 to 300 s (N = 15) and from 40.6 to 104.4 s (N = 15). All of these effects were blocked by pretreatment with naloxone (0.4 mg/kg). Alpha-endorphin (0.2, 1.0 or 5.0 micrograms/kg) administered either after training or before testing had no effect on retrieval. Since at least the amnestic effect of gamma-endorphin is similar to that of beta-endorphin, and gamma-endorphin is a possible metabolite of beta-endorphin by limited proteolysis of the carboxyl-terminal amino acid, it is suggested that at least some effects of beta-endorphin on memory may be mediated by its proteolysis product, gamma-endorphin.

Amnesia↗

PubMed1989

Undernutrition during suckling does not change the specific or total activity of hypothalamic proline endopeptidase in adult rats.

Undernutrition during suckling causes a decrease in hypothalamic beta-endorphin-like immunoreactivity in rats. Since proline endopeptidase (E.C. 3.4.21.26) has been proposed to play a role in the processing of beta-endorphin, we examined the effects of undernutrition during suckling on the enzyme activity. Rats were undernourished by feeding their dams an 8% casein diet from the day of birth until weaning (21 days). Dams of well-nourished rats were fed a 25% casein diet during the same period. After weaning, all rats received a 20% protein diet until 90 to 120 days of age when they were killed for the enzyme assay. The specific and total activity of hypothalamic proline endopeptidase was not altered by undernutrition followed by nutritional rehabilitation (2.37 +/- 0.24 nmol sulphamethoxazole min-1 mg-1 for well-nourished rats vs 2.68 +/- 0.24 nmol sulphamethoxazole min-1 mg-1 for undernourished rats). This lack of correlation suggests that proline endopeptidase is probably not responsible for the low levels of hypothalamic beta-endorphin found in adult rats submitted to undernutrition during suckling.

Animals↗

PubMed1989

Chronic ethanol ingestion selectively affects memory modulation in rats.

Post-training treatment alters memory by different mechanisms. Naloxone enhances memory by antagonism of endogenous beta-endorphin-induced state dependency. Epinephrine facilitates consolidation at low doses and generates state dependency at high doses. Exposure to a session of tones causes retroactive interference through a cognitive effect. The present data show that chronic ethanol ingestion, in rats, inhibited the post-training effect of naloxone and of a high dose of epinephrine on the retention of an inhibitory avoidance task but did not inhibit retrograde interference by a session of tones or retrograde facilitation by a low dose of epinephrine. Therefore, ethanol appears to selectively affect post-training influences related to state dependency.

Animals↗

PubMed1988

Diazepam blocks the interfering effect of post-training behavioral manipulations on retention of a shuttle avoidance task.

Rats were submitted to a training and a test session of shuttle avoidance. Exposure to a session of extinction of this task either 2 or 24 h after training interfered with retention test performance. Exposure to an open field 2, but not 24 h after the avoidance training also interfered with retention. Diazepam blocked the deleterious effect of extinction and of the open field on retention of the avoidance task. Diazepam alone had no effect when given after avoidance training; it did, however, also interfere with retention when given prior to training. It is likely, therefore, that diazepam cancelled the effect of the extinction or of the open field on avoidance retention because of anterograde amnesia (i.e., it prevented the recording of these tasks). The deleterious effect of the open field on retention of shuttle avoidance can be explained by retroactive interference caused by the addition of information. It is not due to a direct influence on retrieval, it is not due to extinction, and it had to be recorded 2 h after training in order to the effective.

Animals↗

PubMed1988

Post-training and pretest effects of adrenocorticotropin on retention: the influence of the hour of the day, the training-test interval, and pretest naloxone administration.

Rats received an ip injection of 0.2 microgram/kg of ACTH-(1-39) 1 min after step-down inhibitory avoidance training and/or 5 min prior to retention testing. Experiments were carried out either in the morning or in the afternoon using either a 3- or a 24-h training-test interval. Post-training ACTH induced memory facilitation in the morning and amnesia in the afternoon at both training-test intervals. Pretest ACTH reversed the afternoon amnesic effect, also at both training-test intervals. In addition, pretest ACTH induced a naloxone-reversible memory enhancement, both on its own and in animals treated with a facilitatory post-training dose of ACTH in the morning; this effect was seen only at the 24-h training-test interval. Naloxone had no effect of its own and did not influence the reversal of ACTH-induced amnesia caused by pretest ACTH in the afternoon. The results point to the variety of memory modulatory influences of ACTH, and to some of the factors involved in the elicitation of one or other effect, namely, the presumable basal rate of secretion of endogenous ACTH, and the previous pharmacological history of the animal.

Adrenocorticotropic Hormone↗

PubMed1988

Memory facilitation by posttraining and pretest ACTH, epinephrine, and vasopressin administration: two separate effects.

Rats were trained in a step-down inhibitory avoidance task using a 0.3-mA, 2-s, 60 Hz footshock and tested 24 hr later. The animals received, 1 min after training and/or 5 min before testing, an ip injection of saline, ACTH (0.2 microgram/kg), lysine-vasopressin (10 micrograms/kg), epinephrine (5 micrograms/kg), naloxone (0.4 mg/kg), or a combination of naloxone with one of the hormones. Both the posttraining and the pretest injection of the hormones enhanced retention test performance; the enhancement was larger in animals that received the two treatments. Posttraining, but not pretest, naloxone administration also caused an enhancement. However, posttraining naloxone potentiated, and pretest naloxone antagonized, the effect of the concomitantly injected hormones. These data show that the posttraining and the pretest effect of the hormones are independent, are due to different mechanisms, and can be additive. In addition, it does not seem possible to explain posttraining memory facilitation by the hormones as owing to an addition to the reinforcement.

Adrenocorticotropic Hormone↗

PubMed1988

Construction and reconstruction of memories.

1. Recent evidence suggests that treatments given after training may influence memory in two ways: by becoming themselves incorporated to the experience, or by altering post-training mechanisms involved in the storage of the experience. The two processes may be called consolidation. 2. Some endogenous substances that are normally released during or after training (brain beta-endorphin; the peripheral stress hormones, ACTH, epinephrine and vasopressin) appear to be of particular importance. Their effect may become incorporated to the experiences as a conditioned stimulus (CS), generating state dependency. The effect of beta-endorphin appears to be physiological, since the substance is released by novel experiences. 3. Post-event information provided by other training experiences, in rats, or by comments or leading words, in humans, may also incorporate to the experiences, altering their content qualitatively or quantitatively. 4. A variety of substances including the stress hormones at low doses and analeptic drugs may facilitate retention when given after training. In this case, the effect is best explained by an enhancement of the post-training strengthening of memory traces. 5. The reiteration of part of the experiences at the time of testing facilitates retrieval. This may be viewed as a reconstruction of consolidation at the time of retrieval, and may be obtained using cognitive material ("priming"), or neurohumoral stimuli (a beta-endorphin injection, or a presumable release of brain beta-endorphin by an interpolated novel experience). The effect can be seen in animals rendered amnestic by electroconvulsive shock, and in humans with amnesia of organic and non-organic nature. 6. The human amnesic syndrome seems, thus, largely explainable by a deficit of retrieval. It is possible that the stimulation of retrieval by priming, or by drugs, through the "reconstruction" of consolidation, may be useful for the relief or treatment of the human amnesic syndrome.

Amnesia, Retrograde↗

PubMed1986

Hypothalamic proline endopeptidase activity is not changed by various behavioral procedures.

Proline endopeptidase (E.C.3.4.21.26) is an enzyme which cleaves several neuropeptides at the carboxyl-side of proline residues. Some peptide substrates of this enzyme may be found in the rat hypothalamus (thyrotropin releasing hormone, neurotensin, substance P, oxytocin, vasopressin, beta-endorphin). Recent research has shown that the hypothalamic levels of some of these substances (e.g., vasopressin, beta-endorphin) change by a variety of training procedures. We studied the effect of various forms of training on the activity of proline endopeptidase of rat hypothalamus. The present results show that the activity of this enzyme is not altered by electroconvulsive shock or inhibitory avoidance training when measured, 0, 1, or 3 hr after these procedures. Other behavioral procedures (habituation to an open field, two-way active avoidance conditioning, or 1 min of inescapable footshock) also had no effect on hypothalamic proline endopeptidase activity measured immediately after training or test sessions. We conclude that proline endopeptidase probably does not play a regulatory role in the effect of synaptically released hypothalamic neuropeptides on behavior.

Animals↗

PubMed1986

Distribution of proline endopeptidase activity in sub-synaptosomal fractions of rat hypothalamus.

1. Proline endopeptidase (E.C.3.4.21.26) is an enzyme which cleaves several peptides at the carboxyl side of proline residues. Because brain contains relatively large amounts of this enzyme and because of its specificity it has been suggested that it plays a role in the metabolism of neuropeptides, acting both on their processing and their degradation. 2. Since the final steps of neuropeptide processing occur in the synaptic vesicles and the degradation of most of these peptides is believed to occur in the synaptic cleft, we studied the distribution of proline endopeptidase activity in sub-fractions of rat hypothalamus. 3. Proline endopeptidase activity is present in synaptosomal fractions and is released by hypo-osmotic shock. Its specific activity is higher in the synaptoplasma than in synaptic membranes or vesicles (7.98 vs 0.18 and 0.24 nmol min-1 mg protein-1 carbobenzoxy-glycyl-prolyl-sulfamethoxazole hydrolysis). 4. Inhibitory avoidance training, a situation which releases hypothalamic vasopressin and beta-endorphin, both in vitro substrates, did not affect the specific or total activity of proline endopeptidase in synaptosomal plasma membranes.

Animals↗

PubMedDate not supplied

Effects of chronic ethanol consumption on gestation and lactation in rats.

Chronic consumption of ethanol during pregnancy and lactation may lead to abnormalities in the fetus or infant. A group of female Wistar rats was submitted to ethanol treatment over a period of a month. A pair-fed control group received sucrose solution isocaloric to ethanol and the control group received water "ad libitum." Afterward, the females were mated with males over a period of 20 days. At birth, each litter was maximized to eight pups and the remaining ones were decapitated to remove the fetal blood and brains. No significant difference was observed in fetal body and brain weight at birth. During lactation the ethanol and pair-fed groups gained less weight than the control group. After weaning, their weight became similar. Fetal blood glucose levels were decreased in the ethanol-treated group. One hundred percent of the pair-fed and control females delivered live fetuses at term and all survived; only 40% of the females in the ethanol group delivered, and one pup did not survive. Chronic ethanol treatment pointed to a possible reduction in the fertility. It seems likely that the change in body weight of ethanol-fed dams was caused by undernutrition.

Alcohol Drinking↗