Biomedical subjects

D Quartermain

Publications and source records attributed to D Quartermain.

At least 37 records · Page 2Linked to original sources

PubMed1993

Effect of propofol on memory in mice.

The amnestic effects of the intravenous hypnotic anesthetic agent 2,6-diisopropylphenol (propofol; Diprivan) were studied in a single-trial passive avoidance task. Mice were injected with propofol 10 min before or immediately after training. Memory was impaired in a dose-dependent fashion when the anesthetic was administered before learning, but no amnesia was apparent with posttraining injections. Examination of the acquisition of passive avoidance using a multitrial task showed that propofol-treated mice learned the response normally but forgot the learning significantly faster than vehicle-treated controls. The anterograde amnesia was not the result of state-dependent learning. Propofol also disrupted extinction of fear conditioning when the anesthetic was given during the extinction session. Propofol-induced amnesia could be attenuated by amphetamine (1 mg/kg) injected 30 min before the retention test.

Amnesia, Retrograde↗

PubMed1993

Effect of the calcium channel blocker amlodipine on memory in mice.

Five experiments were performed to investigate the effects of amlodipine, a calcium channel antagonist of the 1,4-dihydropyridine class, on consolidation and retrieval of memory in mice. In a single-trial passive avoidance task, amlodipine was administered pretraining, posttraining, or pretesting. Results of temporal and dose-response studies showed that memory enhancement (significant increase in step-through latency) occurred when amlodipine (5, 7, 9, 15, and 30 mg/kg) was given either immediately post-training or (15 mg/kg) 15 min pretesting. Using a conditioned emotional response task, tone was paired with shock using Pavlovian conditioning procedures. Strength of conditioning was assessed by measuring suppression of drinking in the presence of a tone. Amlodipine (7 mg/kg) given immediately following both high- and low-intensity shock significantly enhanced conditioned suppression. In the third experiment thirsty mice were trained on a spatial discrimination task in a linear maze. Correct choices were reinforced with liquid reinforcement. Amlodipine (10 mg/kg) injected immediately after the training session produced a significant enhancement of discrimination performance on a 24-h retention test. In the fourth experiment mice were given 25 training trials in a two-way active avoidance task and were treated with either amlodipine (10 mg/kg) or saline after training. Amlodipine-treated mice made significantly more avoidances on the test session than control animals. The final experiment demonstrated that the deficit in approach-avoidance behavior seen in 18-month-old mice could be reversed by amlodipine treatment after the training session. These studies suggest that amlodipine can facilitate memory consolidation and retrieval.

Amlodipine↗

PubMed1993

Selective dorsal rhizotomy: outcome and complications in treating spastic cerebral palsy.

Selective dorsal rhizotomy has shown great promise as a treatment for the functional disabilities and deforming hypertonia of spastic cerebral palsy. At New York University Medical Center, 200 children underwent this procedure between 1986 and 1990. All groups, whether walkers, crawlers, or nonlocomotors, showed improvement in the tone and range of most muscles tested. Half of these patients experienced complications. Thirty-five of these were serious and included bronchospasm (5.5%), aspiration pneumonia (3.5%), urinary retention (7%), and sensory loss (2%). There are, however, clear indications that warn of these complications; monitoring and prophylactic treatment can minimize their effects, and the possibility of such problems is more than offset by the proven benefits of this operative procedure.

Cerebral Palsy↗

PubMed1992

Halothane anesthesia causes state-dependent retrieval failure in mice.

Effects of exposure to halothane on memory processing was studied using single-trial inhibitory avoidance learning to measure retention. Mice were anesthetized with halothane either before training, immediately after training, or both before training and before testing. Results showed that memory was not impaired by posttraining halothane exposure, indicating that the anesthetic does not cause retrograde amnesia. Mice trained after recovery from halothane showed a robust memory loss 24 h later. This deficit could be alleviated by reexposure to the anesthetic before the retention test. Mice given multiple training trials following recovery from the anesthetic showed a normal rate of learning when compared with controls, but deficient retention. This indicates that the performance deficit was the result of impaired retention (anterograde amnesia) rather than disrupted acquisition. Anterograde amnesia occurred when training was delayed up to 2 h after recovery from anesthesia. These findings indicate that the memory impairment following halothane anesthesia is the result of a state-dependent retrieval failure.

Amnesia, Retrograde↗

PubMed1991

Milacemide enhances memory storage and alleviates spontaneous forgetting in mice.

The objective of this study was to evaluate the effectiveness of milacemide as a memory-enhancing drug in mice. Experiment 1 showed that forgetting of active avoidance learning produced by a 14-day training to test delay could be alleviated by milacemide (10 mg/kg) administered before the retention test. Experiment 2 demonstrated that the same dose of milacemide could also attenuate spontaneous forgetting of passive avoidance learning, thereby ruling out nonspecific effects as an explanation for the enhancement of performance following pretesting drug administration. A third experiment showed that the facilitation of retrieval induced by milacemide could be blocked by the NMDA receptor antagonist AP-7, suggesting that the effects of milacemide on memory may be mediated by NMDA receptor activation. A final experiment demonstrated that retention was improved when milacemide was administered immediately following active avoidance training, indicating that the drug can also facilitate remembering by its actions on consolidation and storage processes.

2-Amino-5-phosphonovalerate↗

PubMed1990

Prenatal treatment with a selective D1 receptor agonist (SKF 38393) alters adult [3H]paroxetine binding and dopamine and serotonin behavioral sensitivity.

We have previously shown that the development of serotonin neurons can be affected by various pharmacological agents acting on the serotonin system. Receptor stimulation by high doses of 5-methoxytryptamine (5-MT) causes increased outgrowth, through release of an astroglial growth factor, while a low concentration of 5-MT has a direct inhibitory effect on neuronal outgrowth. Since 5-MT is known to be a release-regulating autoreceptor agonist, the present study was aimed at testing the hypothesis that inhibition of serotonin release causes the inhibition of outgrowth. We used the D1 receptor agonist SKF 38393 as an inhibitor of serotonin release. Pregnant Sprague-Dawley rats were treated with SKF 38393 (1 mg/kg; subcutaneously) from gestational day 12 until parturition. Development of serotonin terminal outgrowth was evaluated in the offspring using the selective uptake marker [3H]paroxetine in brainstem and frontal cortex. In saline and SKF 38393 treated animals, the developmental pattern in the frontal cortex showed the highest terminal density at day 60 and a return to normal by day 90, with no statistically significant differences between the groups. Conversely, in the brainstem, [3H]paroxetine binding developed normally until postnatal day 90, when the SKF 38393 pretreated animals showed only 58% of the binding observed in saline animals. In a fixed interval responding task, given at day 90, both dopamine and serotonin receptor systems have significantly decreased sensitively after the SKF 38393 pretreatment. In conclusion, our results show that the inhibitory effects of serotonin on the growth of serotonin neurons, may be through inhibition of neurotransmitter release. Moreover, we propose a means by which serotonin and dopamine systems could be interdependent during development.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1989

Persistence of retrieval enhancement by amphetamine following scopolamine-induced amnesia.

Little information is available on the permanence of pharmacologically-induced retrieval enhancement following amnesia. This was studied by comparing the rate of forgetting of a memory reactivated by d-amphetamine after amnesia with spontaneous forgetting of undisturbed fear conditioning. Mice were treated with either saline or scopolamine before conditioning and retention was tested three days later. Scopolamine-treated mice received either saline or amphetamine before testing while the saline controls received a second saline injection. The scopolamine-saline group exhibited robust amnesia, whereas both saline-saline and scopolamine-amphetamine groups showed good retention. To test the persistence of these effects mice in the three groups were subdivided and given a second retention test either 1 day, 1 week or 1 month after the first test. Amphetamine was not administered before the second test. The scopolamine-saline mice continued to exhibit amnesia for up to 1 month while the scopolamine-amphetamine and saline-saline groups continued to show strong memory with only a modest decrement in performance by 1 month after the first test. These results show that amphetamine results in a permanent recovery from scopolamine amnesia.

Amnesia↗

PubMed1988

Amphetamine enhances retrieval following diverse sources of forgetting.

The generality of amphetamine-induced retrieval enhancement was investigated by determining whether pretest administration could alleviate different types of forgetting. Thirsty mice were punished for licking a water tube following a period of free drinking. Forgetting of the conditioned drink suppression was induced in different groups of animals by; protein synthesis inhibition, cholinergic receptor blockade, inhibition of norepinephrine synthesis, stimulation of serotonin receptors, electroconvulsive shock, a 2.5 month training to test interval and the use of senescent animals with an endogenous memory defect. Thirty min prior to testing mice were injected with either saline or with 2 mg/kg d-amphetamine sulphate. Results showed that amphetamine produced a highly significant improvement in remembering in all of the forgetting treatment groups. It is concluded that amphetamine can alleviate forgetting caused by widely diverse etiologies probably by activating a nonspecific general retrieval system.

Amnesia↗

PubMed1988

Alleviation of scopolamine amnesia by different retrieval enhancing treatments.

Mice were trained in a one-way active avoidance task to a criterion of 9/10 avoidances. Immediately following training they were injected with scopolamine hydrochloride (1 mg/kg SC) or with saline. Retention was assessed 3 days after training by 5 test trials on which the UCS was not present. Thirty min prior to the test, groups were injected with different doses of arecoline, d-amphetamine sulphate or with saline. Other scopolamine-treated mice were exposed to the CS or the UCS 24 hr prior to the test. The scopolamine-induced amnesia was attenuated by both 0.5 and 1.0 mg/kg arecoline and by 2.0 mg/kg d-amphetamine. Retention was also improved by exposure to the CS and the UCS. These data show that scopolamine amnesia can be alleviated by treatments which activate retrieval processes.

Amnesia↗

PubMed1988

Attenuation of forgetting by pharmacological stimulation of aminergic neurotransmitter systems.

Mice were trained in one-way active avoidance to a criterion of 3/4 avoidances and tested under extinction conditions one week later when substantial forgetting had occurred. Thirty min prior to testing animals were injected with either saline or different doses of drugs which activate the noradrenergic (phenylephrine, salbutamol, clonidine) dopaminergic (L-dopa(Sinemet) transdihydrolisuride, apomorphine) and serotonergic (fluoxetine, 5-methoxy DMT) neurotransmitter systems. Results showed that all agents alleviated forgetting in a dose dependent fashion. Untrained mice treated with the most effective dose of representative drugs from each class did not exhibit avoidance behavior at testing indicating that the improved performance of trained animals was probably not the result of increased activity or other non-memorial effects of the drugs. It was concluded that pharmacological agents which stimulate monoamine systems may improve memory retrieval by activating a non-specific neural system which controls arousal, attention and motor readiness.

Animals↗

PubMed1988

Strength of scopolamine-induced amnesia as a function of time between training and testing.

Variations in the strength of scopolamine-induced amnesia as a function of age of the habit were studied in Swiss Webster mice. Animals were trained in an active avoidance task to a criterion of 9/10 avoidances and immediately following training injected with scopolamine hydrochloride (1.0 mg/kg) or saline. Retention of the avoidance learning was evaluated by testing different groups of animals 1, 3, 7, 10, 14, and 28 days following training. The retention test consisted of five trials in which the CS but not the UCS was presented. Results indicated that saline-treated mice exhibited near-perfect retention up to 14 days post-training with forgetting beginning to be apparent at 28 days. Scopolamine treatment produced strong amnesia in animals tested 1 and 3 days post-training but normal retention in animals tested 7 and 10 days after learning. The amnesia abruptly reappeared at 14 days after which time it remained stable. The marked similarity of the scopolamine retention curve to changes in the strength of memory of discrimination learning in undertrained rats reported by Deutsch suggested that scopolamine resulted in the storage of a weak memory of the avoidance response. To explore this idea further we trained mice to a criterion (4/5) which would result in a weak avoidance response and tested different groups 1, 3, 10, 14, and 28 days following learning. Results showed that strength of the memory of avoidance learning increased up to 10 days and then decreased abruptly at 14 days thus replicating the general shape of the retention curve produced by injecting scopolamine following strong training. These data suggest that scopolamine disrupts processes essential for the formation of durable memories.

Animals↗

PubMed1985

Reversal learning in senescent rats.

The ability of old (24 months) and young (3 months) male rats to reverse a previously acquired discrimination was compared in 5 experiments. The old rats did not need more trials to learn a position habit in a T-maze to obtain water reward, but required more trials to reverse the position habit. The old rats showed a similar deficit in a second, but not in subsequent reversals of the position habit. In a second experiment, old rats were slower in learning to operate one of two levers in an operant chamber to obtain food reward on a CRF schedule, but by the session prior to reaching criterion for acquisition they showed response rates similar to the young animals. When the rats were required to operate the alternative lever to obtain reward, the young rats emitted 70% of their responses during the first reversal session on the newly-correct lever, but the old rats only 35%. Nevertheless, the groups were similar in the number of sessions required to reach a criterion of 95% of responses on the correct lever. In 3 subsequent reversals, old and young rats did not differ nor were there differences in the number of responses in 4 extinction sessions in the rats which had received reversal training. In experiment 3 with old and young rats which had received only acquisition training, old rats emitted fewer responses than young animals during extinction. From these experiments it was hypothesized that the apparent difficulty of old rats in learning a reversal task was due to the low probability of their emitting spontaneously a novel or previously unrewarded response, and not to a difficulty in forming a new association. This hypothesis was tested in two further experiments in which rats were required to learn a brightness discrimination in a T-maze. Old and young rats which had learned and reversed position habits in the T-maze in experiment 1, did not differ in either acquisition or reversal of the brightness discrimination, suggesting that old rats do not differ from young animals in reversal tasks when the motor response requirements for the task are already within the animals' behavioural repertoire. Consistent with this hypothesis, naive old rats were slower than young rats in acquiring a similar brightness discrimination but did not differ in the reversal task.

Aging↗

PubMed1984

Age differences in within-session habituation of exploratory behavior: effects of stimulus complexity.

The effects of age on the habituation of exploratory behavior of 8-month- and 28-month-old male C57BL/NNia mice were examined under three different stimulus complexity conditions. Increases in the degree of stimulus complexity resulted in an attenuation of between-session habituation and an initial disruption of within-session habituation by 8-month-old mice. Although increases in stimulus complexity also resulted in an increase in the overall level of exploration by aged mice, stimulus complexity was not found to have a systematic effect on between- or within-session habituation by aged mice. No between-session habituation was observed in aged mice under any of the stimulus complexity conditions. Further, aged mice exhibited significant within-session increases, rather than decreases, in exploration under each stimulus complexity condition. This disruption of within-session habituation in aged mice was found to persist over four daily test sessions. In view of the specific patterns of exploration by aged mice, the disruption of within-session habituation was attributed to age-related differences in reactivity to the arousal-inducing properties of novel stimuli.

Aging↗

PubMed1983

Recovery of memory following forgetting induced by depletion of biogenic amines.

Following depletion of biogenic amines by reserpine, mice were trained to avoid one compartment of a shuttle box by employing the procedures of Pavlovian fear conditioning. Retention was tested one week later using both an active and a passive measure. A robust amnesia was apparent in reserpine-treated animals on both retention measures. Treatment with the mixed dopamine-serotonin agonist lisuride 30 min prior to the test alleviated the memory loss. Since improved retention in the drug treated mice was indexed by increased response latencies in the passive test and decreased latencies in the active test it is unlikely that the improvement in performance was the result of non-specific effects on activity. The results are consistent with the hypothesis that lisuride treatment before testing facilitates retrieval processes.

Animals↗

PubMed1983

Facilitation of memory retrieval by centrally administered catecholamine stimulating agents.

Amnesia for inhibitory avoidance learning induced in mice by a post-training injection of the protein synthesis inhibitor anisomycin was alleviated in a dose-dependent fashion by introcerebroventricular injections of D-amphetamine (20 micrograms), dopamine (10, 25 and 50 micrograms) and the dopamine agonist lisuride (0.5 and 1.0 micrograms), given 5 min before the retention test. Animals which received avoidance training in a different apparatus did not show increased test latencies following drug treatment thus eliminating non-specific behavioral suppression as an explanation for the findings. Neither norepinephrine nor the norepinephrine agonist clonidine was able to reverse the amnesia. These findings indicate that central dopamine systems may play a role in the retrieval of inhibitory avoidance learning.

Animals↗

PubMed1982

Characteristics of retrograde amnesia following reactivation of memory in mice.

Amnesia for approach-avoidance learning was induced in mice by injecting the protein synthesis inhibitor anisomycin (ANI) immediately, 1, or 2 hours, but not 3 hours after training. A robust amnesia could be demonstrated if ANI was administered 3 hours after training, immediately following a 60 second exposure to the training apparatus or to a structurally similar environment. The temporal gradient of effectiveness of amnesia production by ANI was significantly steeper following reactivation treatment than it was following initial training. In addition, while amnesia produced by the conventional procedure remained stable for 6 days, the amnesia induced following reactivation treatment spontaneously recovered 4 days after training. These findings are discussed in terms of their relevance to interpretations of retrograde amnesia studies.

Animals↗

PubMed1982

Effects of cycloheximide, a protein synthesis inhibitor, on mouse brain catecholamine biochemistry.

Cycloheximide (CXM), a protein synthesis inhibitor, has been shown to result in a marked inhibition of central catecholamine (CA) synthetic mechanisms at doses that cause amnesia in animals. Unlike other inhibitors of CA synthesis no significant depletion of whole brain NE or DA concentrations was observed 0.75, 1, 2, 3, 4, 6, 17, or 24 hours after administration of CXM (120 mg/kg) to C57BL/6J mice. In order to investigate the underlying basis of maintenance of CA levels in face of CA synthesis inhibition, the effects of CXM on in vitro release of 3H-NE was studied in mouse hypothalamic slices. CXM, in a dose related manner, significantly inhibited the potassium stimulated release of NE from hypothalamic slices. Anisomycin, another protein synthesis inhibitor, similarly inhibited NE release. These studies further document the effects of protein synthesis inhibitors on CA mechanisms and suggest that disruption of CA biochemistry may play a role in the amnesia observed after administration of protein synthesis inhibitors.

Animals↗

PubMed1982

Brain cyclic AMP and memory in mice.

A phosphodiesterase inhibitor 4-(3-cyclopentyloxy-4-methoxyphenyl)-2-pyrrolidone (Rolipram, 10 mg/kg IP) administered immediately, but not 3 hr post-training, reversed an amnesia for an inhibitory avoidance response induced by the protein synthesis inhibitor anisomycin. Immediate post-training administration of Rolipram also enhanced retention for a weakly learned avoidance response. Unshocked animals did not show increased test latencies thus ruling out conditioned aversion as an explanation for the enhanced avoidance. Mice treated with Rolipram (10 mg/kg after training showed elevated cyclic AMP but not cyclic GMP in frontal cortex, thalamus, and hypothalamus. These results support the suggestion that cyclic AMP may play a role in memory processes.

Animals↗