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J R Martin

Publications and source records attributed to J R Martin.

At least 55 records · Page 3Linked to original sources
PubMed1997

The solution structure of serine protease PB92 from Bacillus alcalophilus presents a rigid fold with a flexible substrate-binding site.

BACKGROUND: Research on high-alkaline proteases, such as serine protease PB92, has been largely inspired by their industrial application as protein-degrading components of washing powders. Serine protease PB92 is a member of the subtilase family of enzymes, which has been extensively studied. These studies have included exhaustive protein engineering investigations and X-ray crystallography, in order to provide insight into the mechanism and specificity of enzyme catalysis. Distortions have been observed in the substrate-binding region of subtilisin crystal structures, due to crystal contacts. In addition, the structural variability in the substrate-binding region of subtilisins is often attributed to flexibility. It was hoped that the solution structure of this enzyme would provide further details about the conformation of this key region and give new insights into the functional properties of these enzymes. RESULTS: The three-dimensional solution structure of the 269-residue (27 kDa) serine protease PB92 has been determined using distance and dihedral angle constraints derived from triple-resonance NMR data. The solution structure is represented by a family of 18 conformers which overlay onto the average structure with backbone and all-heavy-atom root mean square deviations (for the main body of the molecule) of 0.88 and 1.21 A, respectively. The family of structures contains a number of regions of relatively high conformational heterogeneity, including various segments that are involved in the formation of the substrate-binding site. The presence of flexibility within these segments has been established from NMR relaxation parameters and measurements of amide proton exchange rates. CONCLUSIONS: The solution structure of the serine protease PB92 presents a well defined global fold which is rigid with the exception of a restricted number of sites. Among the limited number of residues involved in significant internal mobility are those of two pockets, termed S1 and S4, within the substrate-binding site. The presence of flexibility within the binding site supports the proposed induced fit mechanism of substrate binding.

Amino Acid Sequence↗
PubMed1997

Synaptic beta-amyloid precursor proteins increase with learning capacity in rats.

The precursor proteins of Alzheimer's disease beta-amyloid peptide, the beta-amyloid precursor protein isoforms, comprise a family of neuronal proteins with synaptic localization whose physiological roles in brain are poorly understood. One possible role for synaptic proteins is involvement in neuronal plasticity. After exposure to an enriched environment compared to impoverished conditions, rats exhibited superior cognitive capacity. Up to approximately four-fold increased overall levels of beta-amyloid precursor proteins were found in cortical/subcortical tissue of the enriched animals displaying significantly more synapses immunoreactive for the different beta-amyloid precursor protein isoforms (beta-amyloid precursor protein695- and beta-amyloid precursor protein751/770) in hippocampus and adjacent occipital cortex. This correlation thus provides in vivo evidence for an association of beta-amyloid precursor proteins with plastic changes induced by complex environment with consequences for cognitive functions and suggests that impaired beta-amyloid precursor protein metabolism at synapses might contribute to brain dysfunction in Alzheimer's disease.

Amyloid beta-Protein Precursor↗
PubMed1997

DMPP-evoked increases in postganglionic sympathetic nerve activity and blood pressure occurs by two mechanisms in the rat.

1. Intravenous administration of the ganglionic nicotinic receptor agonist DMPP (1,1-dimethyl-4-phenylpiperazinium iodide) into urethane-anaesthetized rats evoked dose-dependent increases in mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). 2. The ganglionic nicotinic receptor antagonists pentolinium and hexamethonium either alone or combined did not inhibit the increase in RSNA and MAP evoked by 50 to 200 micrograms kg-1 doses of DMPP. The increase in renal sympathetic nerve activity evoked by DMPP occurred as a brief burst in firing. 3. The increase in MAP, but not RSNA, evoked by DMPP in the presence of pentolinium was inhibited by the selective alpha 1-adrenergic receptor antagonist prazosin. 4. The non-selective alpha-adrenoceptor and NPY receptor antagonist benextramine also inhibited the increase in MAP without inhibiting the increase in RSNA. Surprisingly, the combination of benextramine and pentolinium, or benextramine and hexamethonium, completely blocked the DMPP-evoked increase in RSNA and thus the increase in MAP. 5. The uptake1 antagonist desipramine combined with pentolinium did not affect the DMPP-evoked increases in MAP or RSNA when compared to the responses evoked in the presence of pentolinium alone. 6. Adding the selective M1 muscarinic receptor antagonist telenzepine to pentolinium and prazosin did not inhibit the increase in RSNA evoked by a 100 micrograms kg-1 dose of DMPP. 7. While the DMPP-evoked increase in MAP in the presence of ganglionic nicotinic receptor antagonists is primarily dependent upon activation of alpha 1-adrenoceptors, the increase in RSNA occurs via activation of ganglionic nicotinic receptors and activation of a mechanism susceptible to blockade by benextramine.

Adrenergic Uptake Inhibitors↗
PubMed1996

Deletion of the Herpes simplex 1 internal repeat sequences affects pathogenicity in the mouse.

We have isolated three different herpes simplex virus 1 (HSV-1) recombinant viruses, each frozen in either the P (prototype), IS (inversion of S component), or ILS (inversion of both components) genome arrangement. Common to all three recombinant viruses is the deletion of approximately 14 kilobases (kb) of viral DNA sequences representing greater than 95% of the internal repeat sequences and the insertion of a 9.6 kb mini-Mu genome containing a functional thymidine kinase gene. No unique DNA sequences were deleted from the viral genomes. Analyses of growth curves of the wild-type and recombinant viruses in cell culture has revealed that the recombinants grow somewhat more slowly, producing final titers within 1.5 logs of wild-type HSV-1(F). There is no discernible difference in plaque size or plaque morphology between the recombinant and wild type strains. Analysis of the recombinant viruses in mice reveals the following: I), the recombinant viruses are essentially avirulent, exhibiting drastically increased LD50 values as compared to the wild-type strain by intracerebral injection; ii), the recombinant viruses are not neuroinvasive in that they do not spread from the cornea to sensory ganglion; iii), the recombinant viruses exhibit minimal local replication both in the corneas of infected mice and in the brains of mice inoculated by intracerebral injection; and iv), the recombinant viruses do not establish a reactivable latent infection in the trigeminal ganglion following either intracerebral inoculation or inoculation of scarified corneas. These properties suggest a unique pattern of pathogenesis for HSV mutants in the mouse model.

Animals↗
PubMed1996

A new Drosophila Ca2+/calmodulin-dependent protein kinase (Caki) is localized in the central nervous system and implicated in walking speed.

Calcium/calmodulin-dependent protein kinases (CaM kinases) have been reported to be involved in neuroplasticity. We have cloned a new Drosophila CaM kinase gene named caki. We describe the molecular characterization of caki and a behavioral effect of its elimination. The caki gene is extremely large; comparison of the genomic and cDNA sequences reveals that the caki transcription unit is at least 150 kb. The catalytic domain of this new CaM kinase protein shares homology (41%) with type II CaM kinases, while the C-terminal part is divergent. Constitutively expressed Caki protein is enzymatically active since it causes a 3-fold increase in the level of the Rous sarcoma virus long terminal repeat (RSV LTR) promoter in a co-transfusion assay. In situ hybridization shows that during embryogenesis, larval and pupal life, transcription of caki is restricted almost exclusively to the central nervous system. In the adult head, immunohistochemistry reveals Caki protein in the lamina, the neuropil of the medulla, lobula, lobula plate and in the central brain. Mutant caki flies show reduced walking speed in 'Buridan's paradigm'.

Amino Acid Sequence↗
PubMed1996

beta-APP cognitive function versus beta-amyloid--induced cell death.

The beta-amyloid precursor protein (beta-APP) has been hypothesized to play an important role in the establishment of synaptic connections. Icv injections of anti-beta APP antibodies into rat brains produced no appreciable effect on subsequent learning of a passive avoidance task whereas memory assessed 1 day later in a retention test was impaired in anti-beta-APP--but not control-IgG-injected animals. This suggests a possible involvement of beta-APPs in cognitive functions. In order to evaluate the properties of the proteolytic A beta-fragment accumulating in Alzheimer's disease brains, four different neuronal cell types were exposed to A beta 1-42 for 24 hours. All cells degenerated in response to A beta, yet chromosomal condensation and internucleosomal DNA fragmentation, typical for apoptosis, occurred in only three of the cell types tested. These findings suggest that beta-APPs may play an important role in cognitive processes and additionally, that their alternative proteolytic product A beta may be differentially toxic to neuronal cell types, inducing cell death either by necrosis or by apoptosis.

Amyloid beta-Peptides↗
PubMed1996

5HT2C receptor agonists exhibit antidepressant-like properties in the anhedonia model of depression in rats.

Potential antidepressant properties of preferential 5HT2C receptor agonists were investigated in stress-induced anhedonia, a validated simulation of depression. This simulation evaluates the hedonic state of stressed rats by recording variations in self-stimulation threshold measured before, during, and after exposure to intermittent, unpredictable, mild stressors. This stress regimen gradually elevates self-stimulation threshold, suggesting the development of an anhedonic state. In stressed animals, chronic treatment with the preferential 5HT2C receptor agonists Ro 60-0175 and Ro 60-0332 (3 mg/kg i.p. b.i.d.) prevented the loss of sensitivity to reward. Similarly, when stressed anhedonic animals were curatively treated with Ro 60-0175 (3 mg/kg i.p. b.i.d.), the stress-induced anhedonia was gradually reversed. These results suggest a role for 5HT2C receptors in some aspects of depression, and potential antidepressant properties for selective 5HT2C receptor agonists. Such compounds may offer an innovative approach to the treatment of mood disorders.

Animals↗
PubMed1996

Pressor effect of the putative M1 muscarinic receptor agonist MCN-A-343 in the conscious rat.

The putative M1 muscarinic receptor agonist McN-A-343 evoked a dose-dependent increase in mean arterial pressure (MAP) when administered intravenously to conscious freely-moving rats pretreated with the ganglionic nicotinic receptor antagonist pentolinium. A tachycardia accompanied the increase in MAP which was blocked by the beta-adrenergic receptor antagonist propranolol. The increase in MAP was attenuated by the alpha 1-adrenergic receptor antagonist prazosin combined with the alpha 2-adrenergic receptor antagonist yohimbine. Adding propranolol to alpha-adrenergic receptor blockade uncovered a latent pressor response. Replacing prazosin with benextramine (which blocks NPY in addition to alpha-adrenergic receptors) attenuated the pressor response unmasked by propranolol. This attenuation was comparable to that provided by benextramine of the pressor response to intravenous administration of NPY. Adrenal demedullation only slightly attenuated the pressor response while having no effect on the tachycardia. The catecholamine depletor guanethidine greatly attenuated the McN-A-343-evoked increase in MAP and heart rate. The combination of adrenal demedullation and guanethidine did not further attenuate the increase in MAP but did provide better attenuation of the tachycardia than guanethidine alone. These results show that McN-A-343-evokes an increase in MAP and heart rate of conscious freely-moving rats primarily by causing the release of catecholamines, and possibly NPY, from sympathetic neurons with the adrenal glands playing a minor role.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1996

Behavioral effects of CCKB receptor ligands in a validated simulation of panic anxiety in rats.

Animals or human subjects receiving brain stimulation in the dorsal periaqueductal gray matter (dPAG) show sudden fear-suggestive behavioral reactions and physical signs of autonomic activation which are reminiscent of the symptom profile characterizing a panic attack. An experimental situation in rats measuring dPAG stimulation self-interruption thresholds has been validated as realistically simulating several aspects of panic anxiety with objective signs of symptomatic and predictive validity using established antipanic and panicogenic agents; it was utilized here to evaluate the effects of various cholecystokinin B receptor ligands. A dose-dependent increase in self-interruption thresholds (antipanic-like effect) was recorded following injection of L-365,260 (3.2, 10 and 32 mg/kg i.p.), a CCKB receptor antagonist with good brain penetration, whereas no significant changes in thresholds were recorded following CI-988 (3.2, 10 and 32 mg/kg i.p.), a dipeptoid CCKB receptor antagonist with poor brain penetration. Latencies for self-interruption were not modified, suggesting that motor functions remained intact. No significant changes in self-interruption thresholds were recorded following peripheral administration of the CCKB receptor agonists CCK4 (0.03 to 0.32 mg/kg i.v.; 0.01 to 3.2 mg/kg i.p.) or the metabolically stabilized analog Boc-CCK4 (0.1 to 10 mg/kg i.p.). Systemic administration of the panicogenic compounds caffeine and yohimbine enhance acute anxiety in this model. These data indicate that, in the dPAG simulation of panic anxiety, central CCKB receptor blockade by L-365,260 induces antiaversive effects analogous to those observed following benzodiazepine receptor activation by clonazepam or alprazolam. Potency and efficacy of L-365,260 were lower than those of clonazepam or alprazolam, suggesting modest, but nonetheless authentic, antiaversive properties for this CCKB receptor antagonist. Lack of effects observed following peripheral administration of the agonists CCK4, and Boc-CCK4 or of the dipeptoid antagonist CI-988 is likely to reflect restricted brain penetration of those compounds in rats; it furthermore excludes a contribution of peripheral gastrin and CCKA receptors to the antipanic-like properties of selective CCKB receptor antagonists such as L-365,260.

Animals↗
PubMed1996

Mechanisms of the cardiovascular response to posterior hypothalamic nucleus administration of carbachol.

Unilateral microinjection of the cholinergic agonist carbachol (CCh) into the posterior hypothalamic nucleus (PHN) of conscious rats evoked a dose-dependent increase in mean arterial pressure (MAP). The pressor response was accompanied by tachycardia at all doses of CCh used (0.8-13.2 nmol), although the tachycardia was followed by a secondary bradycardia after the two highest doses (5.5 and 13.2 nmol). To determine the involvement of the autonomic nervous system and arginine vasopressin (AVP) in these cardiovascular changes, we administered selective receptor antagonists intravenously (i.v.) before microinjection of CCh into the PHN. The pressor response evoked by 3.3 nmol CCh could be attenuated by prazosin (an alpha 1-adrenoceptor blocker) or yohimbine (an alpha 2-adrenoceptor blocker) and completely blocked by the combination of prazosin and yohimbine. In contrast, the increase in MAP evoked by 5.5 and 13.2 nmol CCh could be attenuated by prazosin, yohimbine, or D[(CH2)5Tyr(Me)]AVP (AVPX, a V 1-vasopressin receptor blocker), and completely blocked by the combination of prazosin and AVPX. The tachycardia evoked by the 3.3-, 5.5-, and 13.2-nmol doses of CCh could be attenuated by propranolol (a beta-adrenoceptor blocker), and the secondary bradycardia evoked by 5.5 and 13.2 nmol CCh could be attenuated by either methylatropine (a muscarinic receptor blocker) or AVPX. These results suggest that administration of CCh into the PHN increases sympathetic nervous system activity, which increases MAP and heart rate (HR). The increase in MAP activates a baroreflex-mediated bradycardia by increasing vagal tone. This bradycardia is potentiated by an increase in circulating levels of AVP, which also contributes to the increased blood pressure (BP).

Adrenergic beta-Antagonists↗
PubMed1996

Evidence of systemic neuropeptide Y release after carbachol administration into the posterior hypothalamic nucleus.

The unilateral microinjection of the cholinergic agonist carbachol (CCh) directly into the posterior hypothalamic nucleus (PHN) of conscious rats evokes a dose-dependent increase in mean arterial pressure (MAP). Blockade of peripheral alpha-adrenoceptors and V1-vasopressin receptors completely inhibits this response, suggesting that the increase in MAP is mediated by increases in sympathoadrenal excitation and circulating vasopressin. Combining beta-adrenoceptor blockade with alpha-adrenoceptor and V1-vasopressin receptor blockade results in the return of a pressor response. To determine if neuropeptide Y (NPY) might be responsible for this increase, the putative NPY and irreversible alpha 1-adrenoceptor antagonist benextramine was added to alpha 2- and beta-adrenoceptor and V1-vasopressin receptor blockade provided by yohimbine, propranolol, and [D(CH2)5-Tyr(Me)]AVP (AVPX), respectively. Benextramine noncompetitively inhibited the pressor response to intravenous injection of NPY and the increase in MAP evoked by CCh microinjection into adrenergic and V1-vasopressin receptor-blocked rats, whereas benextramine competitively inhibited the pressor response to angiotensin II (AII). Furthermore, the combination of losartan, the selective AT1-AII receptor antagonist that completely blocked the increase in MAP evoked by intravenous AII, and adrenergic and V1-vasopressin receptor antagonists did not attenuate the pressor response evoked by CCh microinjection into the PHN or the increase in MAP evoked by intravenous injection of NPY. These results indicate that AII was not responsible for the CCh-evoked increase in MAP in the presence of adrenergic and V1-vasopressin receptor blockade. The similarity in the antagonism of the increase in MAP evoked by intravenous NPY injection and by CCh microinjection into the PHN of adrenergic- and V1-vasopressin receptor-blocked rats suggests that NPY might be released from sympathetic neurons after activation of the sympathetic nervous system by central administration of CCh into the PHN.

Adrenergic alpha-Antagonists↗
PubMed1996

McN-A-343 increases renal sympathetic nerve activity and blood pressure by a muscarinic and a non-muscarinic mechanism in the rat.

1. Intravenous administration of the putative M1 muscarinic agonist McN-A-343 to conscious rats evokes an increase in mean arterial pressure (MAP) which can be blocked by muscarinic receptor antagonists. The present study was undertaken to evaluate the increase in MAP and renal sympathetic nerve activity (RSNA) evoked by intravenous administration of McN-A-343 to urethane-anaesthetized rats. 2. McN-A-343 (0.1-0.3 mg kg-1) evoked a concurrent increase in MAP and RSNA which could be inhibited by the nonselective muscarinic receptor antagonist methylatropine or the selective M1 muscarinic receptor antagonist telenzepine. Administration of higher doses of McN-A-343 (0.3-1.2 mg kg-1) in the presence of muscarinic receptor blockade evoked brief bursts in RSNA accompanied by increases in MAP. 3. The increases in MAP, but not the increases in RSNA, evoked by all doses of McN-A-343 could be attenuated by the selective alpha 1-adrenoceptor antagonist prazosin. Adding the selective alpha 2-adrenoceptor antagonist yohimbine to prazosin did not further inhibit the pressor response to the low doses of McN-A-343. 4. The irreversible alpha-adrenoceptor and NPY receptor antagonist benextramine also attenuated the pressor response evoked by the low doses of McN-A-343 but not the increases in RSNA. However, when combined with muscarinic receptor blockade, benextramine completely inhibited the brief bursts in RSNA, and thus also the increases in MAP, evoked by the high doses of McN-A-343. 5. The pressor response remaining after the administration of high doses of McN-A-343 to rats pretreated with prazosin and methylatropine was inhibited by treatment with alpha,beta-methylene ATP. 6. These results show that McN-A-343 evokes increases in RSNA by muscarinic and non-muscarinic mechanisms. Furthermore, the subsequent increase in MAP is primarily dependent upon activation of vascular alpha 1-adrenoceptors, but may also involve activation of P2 alpha receptors.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1996

Brain failure in older patients. Uncovering treatable causes of a diminished ability to think.

The term "brain failure" implies only dysfunction of a major organ system, not that an exact diagnosis has been made. Assessment and treatment of older patients with diminished cognitive ability can be challenging; however, the experience can also be extremely rewarding when a reversible condition is alleviated and the patient is given added years of productive life. The first step in patient evaluation is to rule out delirium. The presence of delirium is a medical emergency in a patient of any age. Abrupt onset of cognitive deficit, waxing and waning of symptoms, and worsening of symptoms at night are the hallmarks of delirium. The second step is careful history taking and physical examination to rule out "apparent dementia," a potentially reversible form of brain failure that can mimic irreversible dementia. The third step is to treat what is treatable. Finally, extreme care must be taken in making the diagnosis of true dementia. Diagnosis of such a condition (eg, Alzheimer's disease, multi-infarct dementia, dementia of Parkinson's disease) has a profound effect on the patient and the family. These conditions are largely nontreatable, but physicians still have an important role in helping caregivers find appropriate assistance and support.

Aged↗
PubMed1995

Dorsal periaqueductal gray-induced aversion as a simulation of panic anxiety: elements of face and predictive validity.

Neurosurgical stimulation of the dorsal periaqueductal gray (dPAG) matter in man induces acute signs of autonomic arousal and feelings of subjective anxiety; those signs have phenomenological similarity with the symptom profile characterizing a panic attack. Animals undergoing dPAG stimulation show comparable physical signs of autonomic activation and sudden fear-suggestive behavioral reactions that can be shaped into operant self-interruption behavior. Drugs known to acutely reduce (alprazolam, clonazepam) or precipitate (yohimbine, caffeine) panic attacks in patients were found to acutely and dose-dependently reduce or enhance, respectively, aversion induced by dPAG stimulation in rats. When considered as an animal model of panic anxiety, the dPAG model simultaneously meets criteria of face validity (symptomatic homology) and predictive validity (pharmacological homology under short-term treatment); aspects of its construct validity (theoretical rationale supporting the model) are discussed. It is suggested that dPAG stimulation-induced aversion may represent a model of some aspects of panic disorders.

Alkaloids↗
PubMed1995

The three-dimensional solution structure of human stefin A.

The three-dimensional solution structure of recombinant human stefin A has been determined by a simulated annealing protocol using a total of 1113 distance and angle constraints obtained from 1H and 15N HMR spectroscopy. The solution structure is represented by a family of 17 conformers with an average root-mean-square deviation relative to the mean structure of 0.44 A for backbone atoms and 0.94 A for all heavy atoms for the main body of the structure. The protein has a well-defined global fold consisting of five anti-parallel beta-strands wrapped around a central five-turn alpha-helix. There is considerable similarity between the structural features of free stefin A in solution and the X-ray structure of the homologous protein stefin B in its complex with papain, but there are also some important differences in the regions which are fundamental to proteinase binding. The differences consist primarily of two regions of high conformational heterogeneity in free stefin A which correspond in stefin B to two of the components of the tripartite wedge that docks into the active site of the target proteinase. These regions, which are shown to be mobile in solution, are the five N-terminal residues and the second binding loop. In the bound conformation of stefin B they form a turn and a short helix, respectively.

Amino Acid Sequence↗
PubMed1995

Precipitated withdrawal in squirrel monkeys after repeated daily oral administration of alprazolam, diazepam, flunitrazepam or oxazepam.

The lowest dose of alprazolam, diazepam, flunitrazepam and oxazepam consistently to induce loss of righting reflex in squirrel monkeys or vehicle was orally administered to monkeys on 18 consecutive days: 2 mg/kg alprazolam (n = 4), 30 mg/kg diazepam (n = 4), 1 mg/kg flunitrazepam (n = 4), 280 mg/kg oxazepam (n = 5), or vehicle (n = 4). Tolerance developed rapidly for loss of righting reflex, more slowly for sleep and only minimally for muscle relaxation observed during the period immediately following daily oral administration. Injection of the specific benzodiazepine receptor antagonist flumazenil (10 mg/kg i.v.) 5 h after the ninth daily oral treatment produced signs of precipitated withdrawal (tremor, vomiting and/or convulsions) in one alprazolam-, four diazepam-, one flunitrazepam- and four oxazepam-treated monkeys, but not in the vehicle-treated monkeys. Physiological saline injected intravenously several days later under these same experimental conditions failed to provoke a precipitated withdrawal reaction. When flumazenil-induced precipitated withdrawal was again evaluated after the 18th daily oral treatment, withdrawal signs were observed in all alprazolam- and all diazepam-treated monkeys, as well as in three flunitrazepam- and three oxazepam-treated monkeys, but not in the vehicle-treated monkeys (convulsions were observed in one alprazolam-, two diazepam-, one flunitrazepam- and two oxazepam-treated monkeys). No signs of spontaneous withdrawal were observed in any of the monkeys during a subsequent 3-week drug-free period. Thus, repeated administration of approximately equieffective doses of these four benzodiazepines resulted in a similar development of tolerance and physical dependence (indicated by the occurrence of a precipitated withdrawal reaction).

Administration, Oral↗
PubMed1995

Aniracetam reverses memory impairment in rats.

The pyrrolidinone derivative aniracetam given orally immediately after acquisition of an inhibitory avoidance response reproducibly ameliorated scopolamine-induced amnesia in female rats in an extensive series of test sessions conducted over a 1-year period. In a dose-response experiment it was demonstrated that 50 mg kg-1 was the lowest oral dose of aniracetam to significantly ameliorate scopolamine-induced amnesia. Combined results from these numerous test sessions demonstrated that 50 mg kg-1 aniracetam administered to scopolamine-treated rats resulted in 53% of the animals exhibiting correct passive avoidance responding in the retention evaluation versus 9% of the scopolamine-treated rats given vehicle (in comparison, 64% of the rats injected with vehicle rather than scopolamine in this experimental situation exhibited correct responding in the retention test). There was minimal variation in this pattern of results over the successive 1-month blocks constituting the complete experimental period. Thus, the nootropic compound aniracetam replicably exhibited memory enhancing effects in this animal model of reduced cholinergic function.

Administration, Oral↗