Search PubMed⌕ Search

Biomedical subjects

D J Sanger

Publications and source records attributed to D J Sanger.

At least 73 records · Page 4Linked to original sources
PubMed1995

Effects of typical and atypical antipsychotic drugs on response decrement patterns in rats.

Within-session decrements in instrumental responding are a characteristic effect of certain neuroleptic drugs including haloperidol and pimozide. There is little consensus, however, as to whether these effects can best be explained as motivational or motor deficits. A number of recently developed drugs have been described as atypical antipsychotics and are claimed to produce fewer motor side effects than more traditional neuroleptics. Little work has been done to investigate whether such atypical agents also give rise to within-session response decrements. The present experiment used the operant responding of rats to study the effects of a range of antipsychotic drugs. Rats were trained to lever press for food during daily sessions (FR10 schedule) and responding was recorded during each 3-min period of the 15-min sessions. Dose-related decreases in overall response rates were produced by all the drugs studied; ED50 values were: haloperidol 0.17 mg/kg, risperidone 0.18 mg/kg, setoperone 0.23 mg/kg, remoxipride 1.2 mg/kg, sertindole 4.8 mg/kg, thioridazine 7.6 mg/kg, clozapine 8.9 mg/kg, amisulpride 34 mg/kg, sulpiride 74 mg/kg. The presence of within-session response decrements was confirmed for haloperidol and demonstrated with remoxipride, but similar effects were not observed with clozapine, thioridazine, risperidone, sertindole, setoperone, sulpiride and amisulpride. As a number of these drugs were known to have high affinity for 5HT2 receptors, the effects of the 5HT2 antagonist ritanserin (1 and 10 mg/kg) were studied alone and in combination with haloperidol. Ritanserin had no effect on response rates, and did not antagonize but rather potentiated the effect of haloperidol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Tolerance, cross-tolerance and dependence measured by operant responding in rats treated with triazolam via osmotic pumps.

Previous research has found that drugs with affinity for omega (benzodiazepine) sites differ in their abilities to produce tolerance and dependence. The present study therefore investigated the effects of ligands of omega (BZ) sites in rats that had been rendered tolerant to a benzodiazepine. Two experiments were carried out in separate groups of rats. Behavioral changes induced by chronic infusion of triazolam (3 mg/kg/day, SC, for 14 days) via osmotic pumps were studied in animals trained on a fixed ratio 10 schedule of food presentation. Control animals were implanted with pumps containing the vehicle. Test drugs were administered IP using cumulative dosing. In one experiment triazolam decreased response rates on days 1, 2 and 3 after implantation of the pumps and tolerance developed to this depressant effect. In the other experiment, vehicle and triazolam treated rats differed in their responding during chronic infusion but differences were not statistically significant on any particular day. Flumazenil (3.0-30 mg/kg) greatly decreased rates of responding on day 11 in triazolam treated rats. This effect may represent a precipitated withdrawal syndrome. However, no withdrawal effects on operant performance were observed upon pump removal. Chronic infusion of triazolam did not affect the sensitivity of rats to alpidem on day 11 (10-100 mg/kg) whereas it abolished the stimulant effect of bretazenil (0.1-1.0 mg/kg). Chronic triazolam treatment produced tolerance to the depressant effects of triazolam (1.0-3.0 mg/kg), lorazepam (0.3-3.0 mg/kg) and zopiclone (10 mg/kg) but no tolerance to those of CL 218,872 (3.0-30 mg/kg) and zolpidem (0.3-3.0 mg/kg) when tested 3-14 days after pump removal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Discriminative stimulus effects of alpidem, a new imidazopyridine anxiolytic.

Alpidem in an imidazopyridine derivative which binds selectively to the omega 1 (BZ1) receptor subtype. It is active in some, but not all, behavioural tests sensitive to benzodiazepine anxiolytics and has clinical anti-anxiety effects. However, in a previous study, it was shown that alpidem did not substitute for chlordiazepoxide in rats trained to discriminate this benzodiazepine. The present experiments were carried out to investigate the discriminative stimulus properties of alpidem in greater detail. In the first experiment rats learned to discriminate a dose of 10 mg/kg alpidem from saline. Acquisition of the discrimination was long and performance unstable. Chlordiazepoxide, clorazepate and zolpidem substituted only partially for alpidem but the effects of the training dose of alpidem were blocked by 10 mg/kg flumazenil. The second experiment established stimulus control more rapidly to a dose of 30 mg/kg alpidem. Alpidem induced dose-related stimulus control, and dose-related and complete substitution for alpidem was produced by zolpidem, abecarnil, CL 218,872, triazolam and suriclone. Partial substitution occurred with chlordiazepoxide, clorazepate and pentobarbital. In most cases, high levels of substitution were produced only by doses which greatly reduced response rates even though the training dose of alpidem produced only modest decreases in rates. Ethanol, buspirone and bretazenil produced very little substitution for alpidem and both flumazenil and bretazenil antagonised the effects of alpidem. In two further experiments alpidem was found to substitute for the stimulus produced by zolpidem (2 mg/kg) but not for that produced by ethanol (1.5 g/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Effects of chronic treatment with triazolam on operant responding in rats.

The aims of the present study were to investigate the effect of the benzodiazepine antagonist, flumazenil, on operant responding in rats treated chronically with the short-acting hypnotic triazolam and to study the consequence of chronic triazolam treatment on the time course of effects of triazolam and zolpidem. Zolpidem is an imidazopyridine with a pharmacological and behavioral profile that differs from that of the benzodiazepine hypnotics. Rats were treated with saline or triazolam (1 or 3 mg/kg) twice daily for 5 days and were tested daily 1, 3, 5.5 or 7.5 h after injection. In addition, on the 5th day of chronic treatment all rats were injected with flumazenil (10 mg/kg) 10 min before session. The time course of effects of triazolam and zolpidem was determined after cessation of repeated saline or triazolam treatment. Tolerance to the depressant effect of 1 mg/kg of triazolam developed during long-term administration. Flumazenil decreased operant responding in rats pretreated with triazolam. The effect was statistically significant when rats had received 1 mg/kg of triazolam 3 h before the session or 3 mg/kg of triazolam 3, 5.5 or 7.5 h before the session. After cessation of chronic treatment, rats pretreated chronically with 3 mg/kg of triazolam displayed decreased sensitivity to triazolam and to 10 mg/kg but not 3 mg/kg of zolpidem. The present results indicate that chronic treatment with triazolam induces tolerance to the rate-decreasing effect of the drug and dependence as measured by flumazenil-induced disruption of operant responding. The limited degree of cross-tolerance between zolpidem and triazolam may suggest that their pharmacological mechanisms of action are distinct.

Animals↗
PubMed1994

Recent developments in the behavioral pharmacology of benzodiazepine (omega) receptors: evidence for the functional significance of receptor subtypes.

Recent research in molecular biology has demonstrated the complexity of GABAA receptors and shown that benzodiazepine (BZ-omega) receptor subtypes have a structural reality. It is therefore appropriate to ask whether the different pharmacological effects produced by benzodiazepines (anticonvulsant activity, anxiety reduction, motor incoordination, learning deficits, characteristic discriminative stimulus effects, tolerance and dependence) are associated with activity at different receptor subtypes. The present paper reviews the literature dealing with the behavioral effects of novel BZ (omega) receptor ligands relevant to the question of the functional significance of the BZ1 (omega 1) and BZ2 (omega 2) receptor subtypes. The only drugs currently available with a considerable degree of selectivity are alpidem and zolpidem. These compounds have relatively high affinity for GABAA receptors containing the alpha 1 subunit (corresponding to the BZ1 (omega 1) subtype) and very low affinity for receptors with the alpha 5 subunit (corresponding to one type of BZ2 (omega 2) receptor). Pharmacological effects observed with these, and other, less selective compounds allow several tentative conclusions to be drawn: (a) Little is known of the role of subtype selectivity in anxiolytic or amnestic effects but compounds with low intrinsic activity may reduce anxiety without giving rise to sedation or motor incoordination and BZ1 (omega 1) selective drugs appear to disrupt memory only at sedative doses; (b) Selectivity for BZ1 (omega 1) receptors may be associated with sleep-inducing activity but not with motor incoordination, suggesting that BZ2 (omega 2) receptors may be of particular importance in mechanisms of muscle relaxation; (c) The discriminative stimulus effects of different BZ (omega) receptor ligands are not identical and differences may be related to receptor selectivity; (d) Compounds with BZ1 (omega 1) selectivity and compounds with low intrinsic activity produce little or no tolerance and dependence. A wider range of selective compounds will be necessary to investigate these factors in detail and many different pharmacological profiles can be expected from drugs with selectivity and different levels of intrinsic activity.

Animals↗
PubMed1994

Evaluation of the reinforcing effects of eliprodil in rhesus monkeys and its discriminative stimulus effects in rats.

Two studies examined the abuse potential of the N-methyl-D-aspartate (NMDA) non-competitive antagonist eliprodil [(+/-)-alpha-(4-chlorophenyl)-4-[(fluorophenyl)methyl]-1- piperidineethanol] by evaluating its reinforcing effects in rhesus monkeys and its phencyclidine (PCP)-like discriminative stimulus effects in rats. The monkeys were trained to self-administer PCP i.v. under a fixed ratio 10 schedule of reinforcement. After the monkeys were trained, saline, vehicle and various doses of eliprodil were substituted for PCP. The rats were trained to discriminate 3 micrograms/kg PCP from saline using a standard two-lever discrimination procedure with correct-lever responding reinforced under a fixed ratio 10 schedule of food reinforcement. After acquiring the discrimination, the rats were tested with various doses of PCP, dizocilpine and eliprodil. The self-administration study showed that eliprodil did not have reinforcing effects, since it maintained injection rates comparable to the negative controls, saline and vehicle. In the discrimination study it was found that the higher doses of PCP and dizocilpine resulted in 100% PCP-associated lever responding, whereas eliprodil occasioned no responding on the PCP-associated lever. The results from these studies suggest that eliprodil has a low potential for abuse in humans as well as providing further evidence that eliprodil produces a profile of behavioral effects unlike the PCP-site selective NMDA antagonists.

Animals↗
PubMed1993

Discriminative stimulus effects of omega (BZ) receptor ligands: correlation with in vivo inhibition of [3H]-flumazenil binding in different regions of the rat central nervous system.

Rats can be trained to discriminate benzodiazepines (BZ) from vehicle and there is considerable evidence that the stimulus effects of these drugs are mediated by activity at omega (BZ) modulatory sites of the GABAA receptor complex. A number of recent studies, however, have indicated that differences may exist between the discriminative stimulus effects of benzodiazepines and those of certain non-benzodiazepine ligands for the omega (BZ) receptors (e.g. zolpidem, abecarnil). As it is known that several subtypes of omega (BZ) sites are found in the central nervous system, and that drugs such as zolpidem have selectivity for certain subtypes, it is possible that differential stimulus effects may be associated with receptor selectivity. In the present study, correlations were calculated between the potencies of nine compounds with affinity for omega receptors (diazepam, lorazepam, triazolam, clonazepam, alprazolam, zopiclone, suriclone, CL 218, 872 and zolpidem) to substitute for chlordiazepoxide in rats trained to discriminate a dose (5 mg/kg) of this benzodiazepine and the ability of the same compounds to inhibit the binding of [3H]-flumazenil from different structures in the rat central nervous system in vivo. The correlations obtained were: cerebellum 0.46, cortex 0.39, striatum 0.78 (P < 0.05), hippocampus 0.79 (P < 0.05) and spinal cord 0.95 (P < 0.001). These different structures are known to contain different relative concentrations of omega 1 (BZ1) and omega 2 (BZ2) sites with the spinal cord containing the greatest (80%) and cerebellum the lowest (5%) concentration of omega 2 (BZ2) sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Repeated treatment with alpidem, a new anxiolytic, does not induce tolerance or physical dependence.

Alpidem is a new anxiolytic of imidazopyridine structure which has a high affinity for the omega 1 (BZ1) modulatory site of the GABAA receptor. The present study investigated whether tolerance and physical dependence develop after repeated treatment with alpidem, as is observed with benzodiazepines. Mice were given alpidem (100 mg/kg, p.o.) or diazepam (5 mg/kg, p.o.) twice daily for 10 consecutive days. Tolerance was assessed by measuring antagonism of pentylenetetrazole- and isoniazid-induced convulsions and bicuculline-provoked mortality, following repeated drug treatment. Decreases in the latency to isoniazid-induced convulsions and in the minimal convulsant dose of pentylenetetrazole were taken as an index of physical dependence and were evaluated at different times (3, 6, 14, 42, 67, 96 hr) after drug withdrawal or after flumazenil administration. In addition, changes in sensitivity to the convulsant effect of a beta-carboline (beta-CCM) were measured. Repeated treatment with diazepam produced tolerance to its anticonvulsant activities as indicated by shifts of the dose-response curves by a factor of 3-5. After discontinuation of diazepam treatment, spontaneous withdrawal occurred within 24 hr and lasted 67 hr as indicated by decreases in the threshold for convulsions induced by isoniazid and pentylenetetrazole. Flumazenil-induced withdrawal was observed in both isoniazid and pentylenetetrazole-induced convulsion models. Hypersensitivity of mice to the convulsant effect of beta-CCM also occurred. In contrast, repeated treatment with alpidem did not produce tolerance to its anticonvulsant effects and neither spontaneous nor flumazenil-induced withdrawal was observed in the pentylenetetrazole and isoniazid models. Moreover, withdrawal of alpidem did not induce any change in the convulsant activity of beta-CCM. These differences between alpidem and diazepam may be related to the low level of receptor occupancy during repeated treatment with alpidem because of its selectivity for omega 1 (BZ1) sites and to its moderate intrinsic activity.

Animals↗
PubMed1992

Discriminative stimulus properties of 8-OH-DPAT: relationship to affinity for 5HT1A receptors.

Previous studies have shown that discriminative stimulus control established with the 5HT1A receptor agonist, 8-OH-DPAT, generalizes to other 5HT1A agonists and partial agonists but also to the alpha 2-adrenoceptor antagonist, yohimbine. On the basis of these results it has been proposed that the 8-OH-DPAT cue may be produced by activity at more than one receptor. In the present study rats were trained to discriminate a dose of 8-OH-DPAT (0.05 mg/kg, SC) from saline. Substitution tests showed dose-dependent generalisation with the 5HT1A compounds, buspirone, ipsapirone, MDL 72832 and MDL 73005EF, the alpha 2-adrenoceptor antagonists, yohimbine and idazoxan, and BMY 14802, which is usually described as a sigma ligand. The buspirone metabolite 1-pyrimidinyl piperazine (1-PP) which possesses mainly alpha 2-adrenoceptor antagonist properties produced only partial generalisation which was not dose related. Receptor binding studies showed that all the compounds which substituted for 8-OH-DPAT displaced [3H]-8-OH-DPAT binding to rat hippocampal membranes. Furthermore, there were statistically significant positive correlations between drug affinity for 5HT1A sites and their ED50 values for both substitution for 8-OH-DPAT and potency to decrease response rates. These results are consistent with the view that the 8-OH-DPAT cue, like the ability of the compounds tested to decrease rates of responding, is largely mediated by activity at 5HT1A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

Differential development of tolerance to the depressant effects of benzodiazepine and non-benzodiazepine agonists at the omega (BZ) modulatory sites of GABAA receptors.

In a previous study, it was found that both the benzodiazepine hypnotic, midazolam, and the imidazopyridine hypnotic, zolpidem, which has selective affinity for a sub-population of omega (benzodiazepine, BZ) modulatory sites of GABA(A) receptors, produced similar decreases in rates of food-reinforced lever pressing in rats. However, during 10 days of repeated administration, marked tolerance developed to the depressant effect of midazolam but little tolerance developed with zolpidem. It was found in the present study that, with a within-subject design similar to that used previously, tolerance developed to the response rate-decreasing activity of the benzodiazepine, triazolam and the cyclopyrrolone, zopiclone but not to that of the triazolopyridazine, CL 218,872. In another experiment, using a between-groups design, tolerance developed to the effect of midazolam, even if the injections were not associated with daily test sessions, providing no evidence for a drug-environment interaction. The lack of tolerance to zolpidem was confirmed in two experiments. There was little indication of tolerance to the depressant effect of zolpidem, even after 19 days administration of daily doses, up to 30 mg/kg, a dose 10 times greater than that which completely suppressed responding. These results showed that the extent to which tolerance develops to the effects of drugs with affinity for omega (BZ) modulatory sites can show wide variations which may be related to differences in mechanisms of action.

Animals↗
PubMed1992

Activity of litoxetine and other serotonin uptake inhibitors in the tail suspension test in mice.

Compounds known to selectively inhibit the neuronal reuptake of serotonin are clinically effective antidepressants. However, in a number of the behavioral models used for detecting and analysing antidepressant action these drugs are inactive. The forced swimming test is not consistently sensitive to these drugs but it has recently been reported that a variation of this procedure, the tail suspension test in mice, is sensitive. The present study showed that five compounds previously shown to be selective serotonin uptake inhibitors--fluoxetine, zimeldine, paroxetine, indalpine, and litoxetine--produced dose-related decreases in immobility in the tail suspension test typical of the effects shown by other antidepressants. In separate experiments, fluoxetine, zimeldine, and indalpine decreased locomotor activity at doses similar to those that decreased immobility. In contrast, paroxetine and litoxetine had no effect on locomotion at the dose ranges active in the tail suspension test. These results confirm the sensitivity of the tail suspension test and indicate that serotonin uptake inhibitors probably decrease immobility and reduce locomotor activity through different mechanisms.

Animals↗
PubMed1992

Increased rates of punished responding produced by buspirone-like compounds in rats.

Buspirone has been reported to have effects on punished responding in rats which are considerably smaller and less reliable than those produced by benzodiazepines. A recent study, however, found that buspirone and ipsapirone increased operant responding suppressed by a stimulus which preceded unavoidable shock, suggesting that conditioned emotional response protocols may be more sensitive than punishment procedures. This hypothesis was not supported by the results of the present study. The food-reinforced lever pressing of rats was maintained by a multiple VI schedule with punished and unpunished components. The experimental parameters were similar to those used in the previous conditioned emotional response study. The benzodiazepines, chlordiazepoxide and clorazepate, as well as buspirone (at one dose) and ipsapirone (at several doses), increased rates of punished responding. The 5-hydroxytryptamine-1A receptor ligands 8-hydroxy-2-(di-n-propylamino)tetralin and MDL 73005EF did not reliably produce similar effects, although increased rates of punished responding were seen in some animals. Haloperidol, imipramine and idazoxan did not increase punished response rates. Although the increases in punished responding produced by buspirone were smaller than those produced by chlordiazepoxide and clorazepate, the effect of ipsapirone was quantitatively similar to that of the benzodiazepines.

Animals↗
PubMed1992

Lack of tolerance and physical dependence upon repeated treatment with the novel hypnotic zolpidem.

Zolpidem is a new, short-acting hypnotic of imidazopyridine structure which binds selectively to a subpopulation of receptors involved in the action of benzodiazepines [omega 1 (BZ1) sites of the gamma-aminobutyric acidA receptors]. The present study investigated whether tolerance and physical dependence develop after repeated treatment with zolpidem as is observed with benzodiazepines. Mice were given zolpidem or the benzodiazepine midazolam (2 x 30 mg/kg, p.o.) for 10 consecutive days. Tolerance to central depressant effects (evaluated by recording spontaneous locomotor activity) and to anticonvulsant effects (measured against pentylenetetrazole-, electroshock- and isoniazid-induced convulsions) was assessed 42 hr after the last administration. A decrease in the latency to isoniazid-induced convulsions was taken as an index of physical dependence and was evaluated 3, 6, 14, 24, 42 and 67 hr after the end of chronic drug treatment. Repeated treatment with midazolam produced tolerance to its sedative and anticonvulsant activities as indicated by shifts of the dose-response curves by a factor of 3 to 5. Fourteen hr after discontinuation of treatment, spontaneous withdrawal was observed and lasted 3 days. When flumazenil was given 3 or 6 hr after the final midazolam injection, precipitated withdrawal was observed. In contrast, after repeated treatment with zolpidem, there was no change in its ability to produce sedative and anticonvulsant effects. Moreover, neither spontaneous nor flumazenil-induced precipitated withdrawal was observed in zolpidem-treated mice.

Animals↗
PubMed1991

Effects of NMDA receptor antagonists and sigma ligands on the acquisition of conditioned fear in mice.

Recent studies have shown that several compounds known to act as competitive or non-competitive antagonists of NMDA receptors can disrupt learning in rodents. The present study was carried out to investigate the effects of a range of NMDA antagonists, acting at several sites in the NMDA receptor complex, on the acquisition of learned fear in mice. Dose-related disruptions of learning were produced by the non-competitive antagonists phencyclidine, dizocilpine, dextromethorphan and (+) and (-)N-allylnormetazocine. The (+) enantiomer of N-allylnormetazocine was approximately twice as potent as the (-) enantiomer. The competitive NMDA receptor antagonist, CGS 19755, also blocked the acquisition of learned fear as did the non-specific glutamate antagonist riluzole. In contrast, the anti-ischaemic drugs ifenprodil and SL 82.0715, which probably act as NMDA antagonists through an effect on the polyamine site, had no effect on learning up to doses which substantially reduced locomotion. The sigma receptor ligand DTG was also inactive. These results confirm that both competitive and non-competitive NMDA antagonists disrupt learning but indicate that the extent to which such an effect is observed may depend on the site at which the compounds act within the receptor complex. Activity at sigma receptors is unrelated to the effect on learning.

Animals↗
PubMed1991

Animal models of anxiety and the development of novel anxiolytic drugs.

1. The behavioural effects of classical anxiolytics such as barbiturates and benzodiazepines have been well characterised. However, recent research has been aimed at the development of novel anxiolytics without problems of sedation, muscle relaxation, amnesia and dependence. 2. A number of novel omega (benzodiazepine) receptor ligands with anxiolytic properties have been described including alpidem, bretazenil, suriclone and abecarnil. Although these compounds share some behavioural effects with older anxiolytic drugs, such as increasing punished drinking, they also show many differences. Their novel profiles may be related to low intrinsic activity or to selectivity for omega receptor subtypes. 3. The possibility that novel anxiolytics may be found among compounds active at serotonin receptors remains a strong hypothesis. Compounds, which, like buspirone, are active at 5HT1A receptors may be anxiolytic as may be antagonists at 5HT2 and 5HT3 receptors. All these compounds have behavioural effects which differ from those of benzodiazepines. 4. In order more effectively to screen for and develop novel anxiolytics it will be necessary to refine behavioural models in the light of feedback from the clinic.

Animals↗
PubMed1990

Differences in pharmacological profiles of a new generation of benzodiazepine and non-benzodiazepine hypnotics.

The hypnotics, quazepam (a benzodiazepine), brotizolam (a thienotriazolodiazepine), zopiclone (a cyclopyrrolone) and zolpidem (an imidazopyridine) have a common ability to bind to the benzodiazepine recognition site (omega receptor) within the GABAA receptor. For this reason we compared their pharmacological profiles in mice. All compounds shared anticonvulsant and central depressant effects. However, the sedative activity of zolpidem appeared at much lower doses than did the anticonvulsant and myorelaxant effects but the opposite was observed with the other hypnotics. In contrast to brotizolam, quazepam and zopiclone, zolpidem did not increase food intake in mice placed in a novel environment, indicating that this drug lacks disinhibitory activity. Moreover the efficacy of zolpidem at the GABAA receptor, as indicated by its activity against convulsions induced by the GABA synthesis inhibitor, isoniazid, was much greater than that of other hypnotics. These results suggest that the hypnoselective properties observed with zolpidem might be related to a high selectivity for the omega 1 recognition site of the GABAA receptor coupled with a very high intrinsic activity.

Animals↗
PubMed1990

Psychopharmacological strategies in the search for cognition enhancers.

In order to discover and develop drugs to treat cognitive decline, animal tests are needed which will predict clinical activity. The process of developing such animal models does not differ, in principle, from the approaches used in other areas of psychotropic drug research. One research approach involves attempts to create models homologous with the disorder to be treated. This requires a thorough analysis of the clinical problem and an attempt to reproduce the biological and behavioral aspects of the disorder in animals. Recent studies of the effects of certain brain lesions on learning in monkeys or rats as models of Alzheimer's disease may go some way towards developing an animal model for this disorder. However, it is arguable whether this approach to "modelling" has ever had much success in psychopharmacology. A more pragmatic strategy involves the development of what are sometimes called emperical models, according to which any biological and behavioral test can be used if it provides a reasonable prediction of activity in the clinic. For example, the much used passive avoidance test in rodents does not need to model human cognition if it accurately predicts clinical activity. The extent to which this approach can be used successfully for evaluating cognition-enhancing drugs is discussed in view of the many drugs already marketed as cognition enhancers.

Alzheimer Disease↗