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D Quartermain

Publications and source records attributed to D Quartermain.

At least 19 recordsLinked to original sources
PubMed2001

Pharmacological blockade of brain alpha1-adrenoceptors as measured by ex vivo [3H]prazosin binding is correlated with behavioral immobility.

The present studies examined the relationship between the blockade of central alpha1-adrenoceptors, as measured by ex vivo binding of [3H]prazosin in the cerebral cortex and the inhibition of behavioral activation to a mildly novel environment (cage change). It was found that intraventricular (i.v.t.) terazosin, a saline-soluble alpha1-adrenoceptor antagonist, dose dependently inhibited both ex vivo cortical binding and behavioral activation and that there was a highly significant positive correlation between the two with a slope near unity. Prazosin, a nonsaline soluble antagonist which had to be given intraperitoneally (i.p.), was much less potent at blocking both behavioral activity and cortical ex vivo binding, although it blocked ex vivo binding in the lung, indicating that it was effective peripherally but did not readily enter the brain. Despite this, however, the inhibition of cortical binding and behavioral activation that i.p. prazosin did produce were highly correlated with each other and had a slope near unity as with terazosin, whereas the more potent inhibition of lung binding was less well correlated with behavioral inhibition and had a slope significantly less than one. These results confirm our earlier studies, which have shown that alpha1-adrenoceptor activity is essential for gross and fine motor behavior in the mouse and that prazosin, which is used extensively in behavioral research, has difficulty entering the mouse brain.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2001

Calcium channel antagonists enhance retention of passive avoidance and maze learning in mice.

Although a number of studies have shown that treatment with calcium channel antagonists (CCAs) can ameliorate impairments in learning and memory in aged animals, evidence for a general nootropic effect of CCAs in neurologically normal young adult animals is ambiguous. This study attempts to resolve some of this ambiguity by comparing the effects of several CCAs on retention of passive avoidance learning and acquisition and retention of appetitively motivated spatial discrimination learning in young adult mice. Animals were trained in a step through passive avoidance apparatus and, immediately after training, injected subcutaneously with different doses of nimodipine, nifedipine, amlodipine, flunarazine, diltiazem, or verapamil. Retention was tested 24 h after training. In the maze-learning task mice were treated with the same doses of the aforementioned CCAs immediately after a brief training session in a linear maze and retention was tested 24 h after training. The most effective dose of each agent in the maze-retention experiment was administered to additional groups of animals 1 h prior to training to determine the effects of CCAs on acquisition processes. The effects of central administration of CCAs were examined by intracerebroventricular injection of different doses of amlodipine immediately after passive avoidance training. Results showed (1) all peripherally administered drugs except verapamil facilitated retention of passive avoidance training in a dose-dependent manner, (2) all drugs dose dependently facilitated retention of linear maze learning, (3) all doses of the drugs (except verapamil) which facilitated maze retention also facilitated maze learning, and (4) central administration of the dihydropyridine amlodipine produced a dose-dependent facilitation of the retention of passive avoidance learning. These data indicate that drugs which block calcium channels can enhance retention of two different types of learning in mice.

Animals↗
PubMed2001

The effects of calcium channel antagonists on short- and long-term retention in mice using spontaneous alternation behavior.

The effect of calcium channel antagonists (CCA's) on working and reference memory in mice was studied using spontaneous alternation (SA) behavior in a T maze. Mice were given either one or four forced trials to either the right or the left arm on the training session (T1) followed by a free choice test (T2) at varying intervals after the initial trial. Untreated animals given one forced trial exhibited significantly greater levels of SA than chance at all delay intervals out to 20 min but not at 30, 60, or 180 min. Animals given four forced trials showed significant levels of SA 24 h after exposure but not at 72 h. Additional groups of mice were treated with amlodipine, nimodipine, diltiazem, and verapamil 1 h before T1. Mice given one forced trial were tested 30, 60, or 180 min after T1 while mice given four forced trials were tested 72 h after T1. Results showed that all of the CCA's except verapamil produced significant SA at the 30-min interval and nimodipine and diltiazem also significantly increased SA at the 60-min-delay interval. No significant effects were observed at the 180-min test. In the four trial groups, all of the CCA's with the exception of verapamil produced significant levels of SA at the 72-h interval. These results indicate that representative CCA's from both the dihydropyridine and the benzothiazapine classes can facilitate both short- and long-interval SA, thereby providing further confirmation that CCA's can enhance memory processing in young animals.

Animals↗
PubMed2001

Pharmacological evidence for the role of central alpha 1B-adrenoceptors in the motor activity and spontaneous movement of mice.

Central alpha 1-noradrenergic neurotransmission has been shown to be an important complement of dopaminergic transmission in the control of motor activity but the identity of the responsible alpha 1 receptor subtype has not yet been identified. This was investigated in the present experiment by measuring the effects of intraventricular administration of a series of alpha 1 antagonists varying in affinities for the three known receptor subtypes--1a, 1b and 1d--on active behavior in mice in response to a cage change. It was found that the potency of the drugs to block both gross and small movements correlated highly with published affinities for the cloned 1b receptor but not for those of either the cloned 1a or 1d receptors. It is concluded that central alpha 1B receptors are critically involved in the mediation of the (nor)adrenergic influence on active behavior, a finding which has implications for basic and clinical research in both movement and mood disorders.

Adrenergic alpha-Antagonists↗
PubMed2000

Enoxaparin, a low molecular weight heparin decreases infarct size and improves sensorimotor function in a rat model of focal cerebral ischemia.

Possible neuroprotective effects of the low molecular weight heparin (LMWH) enoxaparin sodium (Lovenox) were evaluated in a rat model of focal ischemia. Male Sprague-Dawley rats were subjected to 90 min of occlusion of the right middle cerebral artery using the intraluminal suture method. Enoxaparin at doses of 0, 10 or 15 mg/kg was administered to groups of rats 1, 8, 24 and 32 h after artery occlusion. Motor impairment was evaluated by performance on the traverse beam and accelerating rotarod tests. Animals were sacrificed 48 h after occlusion and brain sections were stained with 2% 2,3,5-triphenyltetrazolium chloride for determination of infarct volume. Forty percent of the rats receiving 15 mg/kg enoxaparin died as a result of intracranial hemorrhage. Untreated rats exhibited large lesions involving the caudate putamen and much of the cortex. In enoxaparin - treated rats the damage was mainly confined to the caudate putamen. The sensorimotor behavior of the 10 mg/kg enoxaparin group was significantly better than that of untreated animals. Motor performance of the survivors in the 15 mg/kg group was poor due to hypoactivity and weakness resulting from excessive bleeding. These results suggest that LMWH may have a neuroprotective function.

Animals↗
PubMed2000

Chronic administration of the Ca(2+) channel blocker amlodipine facilitates learning and memory in mice.

Acute administration of the Ca(2+) channel antagonist amlodipine has been shown to facilitate memory for several types of learning in adult animals and to improve retention in aging mice. This study reports three experiments investigating the effect of chronic amlodipine treatment on retention in mice. In the first experiment, groups of mice were treated with either amlodipine or vehicle once a day for 14 days prior to training on a spatial discrimination task. Immediately after training, animals were given a single dose of amlodipine or the vehicle and tested for retention 24 h later. Both groups showed facilitated retention, thereby demonstrating that chronic amlodipine treatment did not produce desensitization to the facilitating effects of a post training treatment. In the second experiment, chronic treatments were administered once daily for 14 days beginning 24 h after training on one-way active avoidance and retention was tested on day 15. Results showed that chronic amlodipine attenuated spontaneous forgetting, but surprisingly, a similar enhancement could be achieved by a single treatment administered 1 day after training. In the third experiment, amlodipine was given either before or immediately after 10 daily training sessions in the one-way active avoidance task. Results showed that chronic treatment accelerated rate of learning. These findings confirm the memory facilitating properties of amlodipine under conditions of chronic drug administration.

Amlodipine↗
PubMed1999

Alpha-1-noradrenergic neurotransmission, corticosterone, and behavioral depression.

BACKGROUND: Impaired brain alpha-1 noradrenergic neurotransmission has been implicated in some of the symptoms of depressive illness but has been difficult to investigate experimentally because of the insensitivity of current animal models of depression. The present experiment addressed this problem by examining the effects of pharmacologic blockade and corticosteroid-induced desensitization of alpha-1 receptors on two newer, more sensitive models in mice: the inhibition of nest-leaving and the tail suspension tests (TST). METHODS: Male mice were administered either prazosin, betaxolol, atipamezole, corticosterone, or repeated restraint stress prior to measurement of either nest-leaving or TST. General behavioral function was assessed in horizontal wire, swim, and latency to escape footshock tests. RESULTS: Prazosin increased depressive behavior in the nest-leaving and TSTs, whereas corticosterone and restraint stress did so only in the more sensitive nest-leaving test. Betaxolol also reduced nest-leaving, suggestive of an alpha-1 beta-1 receptor synergy. The effects of these agents could not be attributed to hypotension, sedation, or general behavioral impairment. CONCLUSIONS: The fact that a reduction in alpha-1 noradrenergic neurotransmission increases depressive behavior, coupled with the fact that this change can result from elevated corticosteroid secretion, provides further support for a role of this factor in depressive illness. As not all alpha-1 functions are reduced in depression, it is likely that only a subgroup or specific locality of alpha-1 receptors are affected.

Adrenergic alpha-Antagonists↗
PubMed1999

Brain alpha 1-adrenergic neurotransmission is necessary for behavioral activation to environmental change in mice.

Terazosin, a water-soluble alpha 1 antagonist that can be administered in high doses intraventricularly was used to study the relationship between brain alpha 1 adrenoceptor neurotransmission and behavioral activation in the mouse. The antagonist was found to produce a dose-dependent, complete inhibition of motor activity and catalepsy which were reversed preferentially by coinfusion of an alpha 1 agonist (phenylephrine) compared to a D1 (SKF38393) or a D2 agonist, (quinpirole). Blockade of central beta-1 (betaxolol), alpha-2 (RX821002) or beta-2 (ICI 118551) adrenoceptors had smaller or non-significant effects. Terazosin's selectivity for alpha 1 receptors versus dopaminergic receptors was verified under the present conditions by showing that the intraventricularly administered antagonist protected striatal and cerebral cortical alpha 1 receptors but not striatal or cortical D1 receptors from in vivo alkylation by N-ethoxycarbonyl-2-ethoxy-1, 2-dihydroxyquinoline. That its effect was due to blockade of brain rather than peripheral receptors was shown by the finding that intraperitoneal doses of terazosin three to 66 times greater than the maximal intraventricular dose produced less behavioral inhibition. Intraventricular terazosin also produced hypothermia and a reduced respiratory rate suggestive of a reduced sympathetic outflow. However, external heat did not affect the inactivity, and captopril, a hypotensive agent, did not mimic it. Terazosin did not impair performance on a horizontal wire test or the ability to make co-ordinated movements in a swim test suggesting that its activity-reducing effect was not due to sedation and may have a motivational or sensory gating component. It is concluded that central alpha 1-noradrenergic neurotransmission is required for behavioral activation to environmental change in the mouse and may operate on sensorimotor and motivational processes.

Adrenergic alpha-Agonists↗
PubMed1997

Greater behavioral effects of stress in immature as compared to mature male mice.

The effect of sexual maturity on behavioral effects of stress was examined in male mice. Immature (4-week-old) or mature (8-week-old) animals were subjected to either social stress (exposure to an isolated adult male) or restraint stress for 5 days and examined for body weight, food intake, or plus-maze behavior. Social stress reduced food intake, body weight, and open-arm entries in 4-week-old but not 8-week-old mice. Restraint reduced body weight in 4-week-old but not 8-week-old mice. It is concluded that immature male mice show greater behavioral disturbances after stress than their mature counterparts. The findings are in agreement with much anecdotal evidence that children are more vulnerable to stress than adults.

Aging↗
PubMed1997

The Effect of Stress on Spontaneous Nest Leaving Behavior in the Mouse: An Improved Model of Stress-Induced Behavioral Pathology.

The present experiments were conducted to develop a more sensitive and reliable model of stress-induced behavioral pathology in the mouse. Male mice were housed singly in nest cages connected to either a circular tunnel, a recreational cage or a large box with food foraging apparatus. Spontaneous nocturnal out of nest activity or food foraging behavior in these environments was continuously monitored for a two week period during which time the effects of stress were examined. It was found that both repeated restraint and aggression stress markedly and persistently reduced out of nest nocturnal activity or food foraging behavior in all 3 environments but did not alter activity in a novel open field or plus maze or food or saccharin intake in the nest cage. In a preliminary experiment the reduction in out of nest activity by stress was attenuated by prior chronic treatment with the antidepressant, desmethylimipramine. Plasma corticosterone was elevated immediately after aggression stress but reduced 5 hr after chronic aggression stress. The reduction in activity did not appear the result of increased anxiety as measured by spontaneous risk assessment behavior in the nest. It is concluded that the decrease in out of nest activity after stress in the present studies models a withdrawn behavioral state and may be due to either or both a decrease in appetitive motivation to leave the nest or an increased aversion to the external environment which does not apparently involve anxiety.

Journal Article↗
PubMed1996

Delayed arousal from anesthesia: a further similarity between stress and beta-1 adrenoceptor blockade.

The present studies investigated the role of beta adrenergic receptors in mediating arousal from anesthesia and the effects of stress on this process. In support of previous findings by others, it was found that blockade of beta-1 and beta-2 receptors by propranolol delayed arousal from halothane anesthesia and that this effect was attributable to blockade of beta-1 receptors because it was duplicated by betaxolol but not by ICI 118,551. Restraint stress also produced a delay in arousal from both halothane and hexobarbital anesthesia. This effect, which was observed at 0.5 but not 24 h after the stress, could not be explained by a stress-induced alteration in the metabolism of the anesthetic, as no difference in brain concentration of hexobarbital was found between stressed and control mice. The parallel effects of beta-1 blockade and stress further supports the hypothesis that stress produces an impairment in function at either the beta-1 receptor or some process coupled to this receptor.

Adrenergic beta-1 Receptor Antagonists↗
PubMed1996

Blockade of effect of stress on risk assessment behavior in mice by a beta-1 adrenoceptor antagonist.

Previous studies have shown that acute stress impairs risk assessment behavior in mice. The present study was undertaken to determine the role of beta adrenoceptors, which are known to be stimulated by stress, in this effect. Mice were treated with either a beta-1 antagonist, betaxolol, a beta-2 antagonist, ICI 118551, an alpha-1 antagonist, prazosin, or an alpha-2 antagonist, yohimbine, and 30 min later were subjected to a 1-h session of restraint stress. Thirty minutes after the stress the animals were tested for the entry latency, number of headpokes prior to entry, and the path of entry into a white open field from a small dark box. In agreement with previous findings, stress was found to markedly reduce risk assessment behaviors as reflected by a reduced entry latency, a reduced number of headpokes and a changed entry path from wall hugging to central entry. Betaxolol was found to prevent all of the above effects of stress dose dependently, whereas ICI 118551, prazosin, and yohimbine had no reversal effects. It is concluded that beta-1 receptor activation and possibly brain glycogen depletion is involved in the effects of stress on risk assessment behavior.

Adrenergic beta-1 Receptor Antagonists↗
PubMed1995

Beta adrenoceptor blockade mimics effects of stress on motor activity in mice.

Reduced central noradrenergic function has been implicated as a factor in reduced behavioral activity after stress. The present studies examined the role of reduced beta adrenergic neurotransmission in mediating this effect. This was done by testing the ability of beta receptor antagonists to mimic the behavioral actions of stress. Mice were subjected to stress or given various beta antagonists and tested for swimming behavior, locomotor activity, or grooming behavior. As previously reported, stress reduced swimming and locomotor activity and increased grooming. Both the nonselective antagonist, l-propranolol, and the beta-1 selective antagonist, betaxolol, produced the same effects as stress on all three measures. A beta-2 selective antagonist, ICI 118,551, was effective only on swimming, whereas a membrane stabilizing agent, d-propranolol, was effective only on grooming behavior. The peripherally active beta-1 antagonist, atenolol, was not effective on any measure. The nonspecific dopaminergic receptor blocker, fluphenazine, reduced locomotion but tended also to reduce grooming. The results indicate that blockade of beta-1 receptors in the CNS selectively mimics the action of stress on gross motor activity in mice and, along with previous data, suggest that stress leads to a relative deficiency in central beta-1 noradrenergic neurotransmission in these animals.

Adrenergic beta-Antagonists↗
PubMed1994

Acute but not chronic activation of the NMDA-coupled glycine receptor with D-cycloserine facilitates learning and retention.

The memory-enhancing potential of D-cycloserine (cycloserine) a partial agonist at the glycine recognition site on the NMDA receptor, was evaluated in mice using a thirst-motivated linear maze learning task. Immediate acute post-training injections (10, 20 and 80 mg/kg) significantly improved retention relative to vehicle-injected controls. Retention was also facilitated if cycloserine (3 and 10 mg/kg but not 20 or 40 mg/kg) was administered 20 min before the retention test. Acquisition of the habit was accelerated if cycloserine (3 mg/kg) was injected 20 min before the training session. Acute post-training injections failed to facilitate retention if mice were pretreated with cycloserine (3 mg/kg) b.i.d. for 15 days before training on the maze. These results indicate that acute cycloserine administration can enhance consolidation and retrieval of memory but that desensitization may occur with chronic exposure to the drug.

Analysis of Variance↗
PubMed1994

The 5-HT1A agonist tandospirone disrupts retention but not acquisition of active avoidance learning.

To determine the effects of the 5-HT1A partial agonist tandospirone on acquisition and retention, mice were trained on a one-way active avoidance task and tested for retention 24 h later. Groups of mice were injected with either saline or 1, 5, or 10 mg/kg tandospirone 30 min before acquisition. Training was complete when animals achieved a criterion of five avoidances in a block of six trials. Results showed that tandospirone did not alter the rate of acquisition of the avoidance response, but retention was significantly disrupted by the 1- and 5-mg/kg doses. These findings confirm previous suggestions that 5-HT1A agonists can cause anterograde amnesia.

Animals↗
PubMed1993

5-HT1A receptor agonists induce anterograde amnesia in mice through a postsynaptic mechanism.

The effect of the 5-HT1A receptor partial agonist tandospirone on memory was investigated in mice using a single trial, step-through passive avoidance task. Tandospirone disrupted performance in a dose-dependent manner when administered before the training trial but not when injected immediately post-training. The pre-training effect was not the result of reduced responsiveness to foot shock because tandospirone did not alter current threshold intensity to elicit flinch, run and vocalization responses. The performance deficit was alleviated by treatment with d-amphetamine prior to the retention test. The memory impairment by tandospirone was mimicked by the 5-HT1A receptor agonist 8-OH-DPAT (8-hydroxy-dipropylaminotetralin HBr) and blocked by the 5-HT1A receptor antagonist BMY7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspirol-[4]- decane-7,9-dione). BMY7378 alone was ineffective. Treatment with the 5-HT synthesis inhibitor PCPA (parachlorophenylalanine) resulted in apparent enhancement rather than disruption of the avoidance behavior. However, the anterograde amnestic effects of tandospirone and 8-OH-DPAT were not affected by PCPA, and lack of interactions between PCPA and the 5-HT1A agonists revealed in the statistical analyses indicated that the effects of PCPA were not mediated by 5-HT1A receptors. It is concluded that 5-HT1A receptor agonists and partial agonists produce a reversible anterograde amnesia that is mediated by postsynaptic 5-HT1A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

5-HT1A agonists disrupt memory of fear conditioning in mice.

A series of experiments was carried out to analyze the effects of the 5-HT1A agonists tandospirone or buspirone on the retention of fear conditioning in mice. Fear was produced by pairing tone and shock in a conditioned emotional response (CER) paradigm and strength of conditioning was assessed by measuring suppression of drinking in presence of tone. Fear conditioning was disrupted if tandospirone and buspirone were administered before the conditioning session but not before the test trial. Diazepam disrupted conditioning at both times. Tandospirone did not disrupt performance if conditioning was tested 1 hr rather than 24 hr after training, suggesting that disrupted memory rather than impaired acquisition was responsible for the deficit. The effect of tandospirone on fear conditioning could be reversed by administration of d-amphetamine prior to the retention test, which suggests that information was stored but is inaccessible to normal retrieval cues. Tandospirone and buspirone also retarded extinction, a clear indication that the disruption caused by these drugs is unrelated to their anxiolytic action.

Analysis of Variance↗