PubMed Health⌕ Search

Biomedical subjects

D Quartermain

Publications and source records attributed to D Quartermain.

At least 19 recordsLinked to original sources
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↗
PubMed1979

Clonidine reverses the amnesia induced by dopamine beta hydroxylase inhibition.

The role of noradrenergic (NE) mechanisms in amnesia induced by the dopamine-beta-hydroxylase (DBH) inhibitor, diethyldithiocarbamate (DEDTC) was examined by studying the antiamnestic characteristics of the alpha-NE receptor stimulator clonidine. DEDTC (250 mg/kg) administered 3 hr prior to training to C57BL/6J mice resulted in marked deficits when retention of a multiple trial food motivated spatial discrimination task was measured 24 hr after learning. Investigation of the temporal aspects of recovery indicated that the agonist was an effective antiamnestic agent when administered 0, 1, 3, 21 and 23 hr after training. No recovery was observed when the drug was administered 6 and 18 hr posttraining. A dose response study of the effectiveness of clonidine administered 1 hr prior to testing indicated recovery of memory at doses ranging from 10-500 microgram/kg. The clonidine induced recovery was not a result of general performance facilitation, but specific to the memory tested. In addition, the clonidine effect was pharmacologically specific to its actions on NE receptors, as recovery was blocked by pre-treatment with the alpha-NE antagonist, phentolamine. No recovery from DEDTC induced amnesia was seen with post-training or pre-test injection of d-amphetamine.

Amnesia↗
PubMed1977

Some characteristics of amnesia induced by FLA-63 an inhibitor of dopamine beta hydroxylase.

The amnesic effects of FLA-63, a potent dopamine-beta-hydroxylase (DBH) inhibitor, were investigated in a food motivated spatial discrimination task. Groups of C57BL/6J mice were injected with either 5 mg/kg, 15 mg/kg, 25 mg/kg, 35 mg/kg or physiological saline 4 hr prior to training. Amnesia was observed 24 hr following training at all dose levels except 5 mg/kh. The performance deficit was specific to memory of the discrimination and not the result of state-dependency. Training conditions which produce an increase in habit strength prevented the amnestic effects of FLS-63. Spontaneous recovery of memory occurred 48 hr following drug administration. Recovery from amnesia was also induced by injections of a monoamine oxidase inhibitor, pargyline, administered 2 hr prior to the retention test. These data suggest that amnesia induced by norpinephrine (NE) depletion is the result of impairment of mechanisms necessary for memory retrieval.

Amnesia↗
PubMed1977

Reversal of cycloheximide-induced amnesia by adrenergic receptor stimulation.

Amnesia for a multiple trial appetitive spatial dicrimination habit induced by the protein synthesis inhibitor cycloheximide (CXM) was reversed by peripheral injections of both alpha (clonidine) and beta (isoproterenol) norepinephrine receptor stimulators. Stimulation of dopamine receptors with piribedil and acetylcholine receptors with pilocarpine was ineffective in reversing amnesia. The clonidine-induced recovery was blocked by phentolamine and the isoproterenol recovery by propranolol. Examination of the temporal parameters of clonidine-induced recovery indicated that the amnesia was prevented if the agonist was injected either before training and CXM treatment, up to 1 hr after training and up to 3 hr prior to testing. Clonidine also alleviated amnesia induced by another protein synthesis inhibitor anisomycin, for a shock motivated brightness discrimination habit. These data suggest that the transient amnesia induced by CXM may be a consequence of disruption of adrenergic mechanisms and more specifically that norepinephrine may play an important role in memory retrieval.

Amnesia↗
PubMed1975

Role of the biogenic amines in the reversal of cycloheximide-induced amnesia.

Amnesia was induced by pretraining injections of cycloheximide (CYC) in a food motivated discrimination reversal task. Magnitude of amnesia varied as a function of the amount of training on both the initial discrimination and the reversal and also as a function of the length of intertrial interval used on both the reversal and the test. Memory spontaneously recovered 48 hr. following reversal training. Recovery from amnesia was induced by pretesting injections of d-amphetamine and 2 monoamine oxidase inhibitors, pargyline and catron. This enhanced performance was a true recovery of the memory and not a result of enhanced learning or increased arousal. Depletion of catecholamines by alpha-methyl-para-tyrosine, a tyrosine hydroxylase inhibitor, and diethyldithiocarbamate, a dopamine beta hydroxylase inhbitor, resulted in an amnesia quantitatively and qualitatively similar to amnesia induced by CYC. These data support the hypothesis that CYC-induced amnesia is mediated via central catecholamines.

Amnesia↗
PubMed1975

Effect of age of habit on susceptibility to cycloheximide-induced amnesia in mice.

The amnesic effects of cycloheximide (CYC) on habits of different ages were investigated in a food-motivated, discrimination-reversal task. Groups of C57BL/6J mice were injected 30 min before training or immediately, 3 days, 6 days, or 9 days after training. Retention was tested 24 hr after CYC treatment. The usual amnesic effect of CYC occurred in animals injected before training. No amnesia was apparent in groups injected immediately, 3 days, or 9 days after training. However, a reliable and reproducible amnesia occurred in the group injected 6 days after training. This amnesia could be reversed by pretest treatment with a monoamine oxidase inhibitor, pheniprazine. Pheniprazine, given 7 days after training, also enhanced retrieval of memory in saline-injected mice.

Amnesia↗