Biomedical subjects

R J Rodgers

Publications and source records attributed to R J Rodgers.

At least 73 records · Page 4Linked to original sources

PubMed1997

Dopamine D4 receptor and anxiety: behavioural profiles of clozapine, L-745,870 and L-741,742 in the mouse plus-maze.

The dopamine D4 receptor has been implicated in the therapeutic effects of the atypical antipsychotic, clozapine. As it has been proposed that anxiolytic-like activity may contribute to the efficacy of this agent in ameliorating the negative symptoms of schizophrenia, the current study employed ethological methods to fully characterize the acute behavioural profiles of clozapine and two more selective dopamine D4 receptor antagonists, L-745,870 (3-[{4-(4-chlorophenyl)piperazin-1-yl)]methyl}-1 H-pyrrolo[2,3b]pyridine) and L-741,742 (5-(4-chlorophenyl)-4-methyl-3-(1-(2-phenylethyl)piperidin-4-yl)is oxazole), in the mouse elevated plus-maze test. Results showed that while clozapine (0.3-6.0 mg/kg) dose-dependently inhibited all active behaviours (arm entries, exploration, rearing) and increased grooming and immobility, it failed to alter the major anxiety indices (percent open entries and open time). In contrast, L-745,870 (0.02-1.5 mg/kg) and L-741,742 (0.04-5.0 mg/kg) did not produce any significant behavioural changes under present test conditions. These data, which contrast markedly with the robust anxiolytic profile of the reference compound, chlordiazepoxide (10.0 mg/kg), provide little support for the suggestion that clozapine possesses anxiolytic-like properties and further indicate that selective dopamine D4 receptor antagonists are ineffective in the modulation of anxiety-related behaviours in the plus-maze.

Animals↗

PubMed1997

Anxiolytic-like profile of p-MPPI, a novel 5HT1A receptor antagonist, in the murine elevated plus-maze.

Recent research on the effects of selective 5-HT1A receptor antagonists in animal models of anxiety has yielded inconsistent findings. In the present study, the behavioural effects of the novel 5-HT1A receptor antagonist, 4-(2'-methoxy-phenyl)-1-[2'-(n-2"-pyridinyl) -p-iodobenzamido]-ethyl-piperazine (p-MPPI), were examined in male mice using an ethological version of the elevated plus-maze test. Results show that at lower doses (0.5-4.5 mg/kg), p-MPPI produced a significant and dose-related anxiolytic profile on both conventional (open arm avoidance) and ethological (risk assessment) measures. However, these effects were lost at a higher dose (13.5 mg/kg) which, instead, increased grooming and immobility. The behavioural profile of p-MPPI is contrasted with those previously obtained with other 5-HT1A receptor ligands (agonists, partial agonists and antagonists), and it is suggested that 5-HT1A receptor antagonists may possess therapeutic advantages in anxiety disorders.

Aminopyridines↗

PubMed1997

Differential effects of chlordiazepoxide on aggressive behavior in male mice: the influence of social factors.

The present study examined the influence of prior social experience on the effects of chlordiazepoxide (CDP; 5.0, 10.0 and 20.0 mg/kg) on intrasexual aggression in male mice. Prior to drug testing, animals were either individually housed or screened in dyadic encounters in a neutral cage. This novel method yielded four experimental groups comprising animals with different social experiences and different aggressive/defensive characteristics: 1) individually-housed males (I): 2) aggressive males (A); 3) counter-attacking males (C), which actively responded to but did not initiate attack; and 4) defeated males (D). Twenty-four hours after screening, animals were treated with CDP and subjected to a resident-intruder test with untreated intruders. Results indicated that the lowest dose of CDP (5 mg/kg) increased aggressive behaviour but only in A males. At higher doses (10-20 mg/kg), CDP reduced attacks towards intruders in A, C and I, but not D, males. In A and C males, the antiaggressive action of CDP was associated with a prosocial effect (increased social investigation), whereas in I males, reduced aggression was associated with an increase in fear-related behaviours. As these differential effects of CDP on intermale aggression cannot be fully explained by differences in behavioural baselines, present data highlight the importance of experiential background as a powerful variable in determining behavioural responses to benzodiazepines. Present findings therefore suggest that an understanding of drug effects on social behaviour demands consideration of biological variability in phenotype.

Aggression↗

PubMed1997

Comparative behavioural profiles of buspirone and its metabolite 1-(2-pyrimidinyl)-piperazine (1-PP) in the murine elevated plus-maze.

It has been suggested that in vivo formation of the metabolite 1-(2-pyrimidinyl)-piperazine (1-PP) may be a major drawback in the use of buspirone as an anti-anxiety agent. To test this hypothesis, the effects of buspirone, alone or with proadifen (an inhibitor of liver microsomal enzymes) pretreatment, were contrasted with those of 1-PP in the murine elevated plus-maze test of anxiety. At 3.0 mg/kg (but not lower doses), buspirone per se had modest anxiolytic-like effects (increased percentage of open arm entries; reduced stretched-attend postures and flatback approach) that were associated with increased grooming and immobility. However, in proadifen-pretreated mice, buspirone produced behavioural depression only, with marked effects evident both at 1.0 and 3.0 mg/kg. As proadifen blocks the biotransformation of buspirone to 1-PP, these data suggest that any anxiolytic activity of buspirone in the murine plus-maze may be attributable to its principal active metabolite. Consistent with this hypothesis, 1-PP (0.5-13.5 mg/kg) produced dose-dependent anti-anxiety effects on both conventional and ethological measures that were not confounded by motoric impairment. Results are discussed in relation to biochemical and electrophysiological studies suggesting that 1-PP has a direct action at 5-HT1A receptors.

Animals↗

PubMed1997

Behavioural effects in mice of subchronic buspirone, ondansetron and tianeptine. I. Social interactions.

In a continuation of recent work on effects of a benzodiazepine (chlordiazepoxide) and selective monoamine reuptake inhibitors (maprotiline and fluvoxamine), the current study compares effects of the 5-HT1A receptor partial agonist, buspirone (0.75-3.0 mg/kg), the 5-HT3 receptor antagonist, ondansetron (0.1-100 micrograms/kg) and the novel antidepressant, tianeptine (2.5-10.0 mg/kg). Compounds were given daily to mice for 21 days prior to testing and the subsequent behaviour of the animals during social interactions was assessed by ethopharmacological procedures. Buspirone, at 0.75 mg/kg, increased immobility and reduced occurrence of the aggressive act, "attack." At 1.5 and 3.0 mg/kg, it enhanced olfactory exploration of the sawdust substrate, but had no effect on social investigation. Ondansetron increased the duration of environmental exploration at 0.1 microgram/kg, while at 100 micrograms/kg it increased the duration of digging in the substrate. Ondansetron had no effect on the categories of behaviour and failed to induce an anxiolytic-like enhancement of social investigation. Tianeptine produced an anxiogenic-like effect at 10 mg/kg, while at 5 mg/kg it enhanced flight and immobility. The relevance of these findings is discussed in relation of the reported behavioural actions of these compounds and to current pharmacotherapy of anxiety and depression. The apparent anxiogenic effect of tianeptine is a novel finding which requires further study.

Animals↗

PubMed1997

Behavioural effects in mice of subchronic buspirone, ondansetron and tianeptine. II. The elevated plus-maze.

In follow-up to recent work on benzodiazepines (chlordiazepoxide) and selective monoamine reuptake inhibitors (maprotiline and fluvoxamine), the present study compares the effects of the 5-HT1A receptor partial agonist, buspirone (0.75-3.0 mg/kg), the 5-HT3 receptor antagonist, ondansetron (0.1-100 micrograms/kg), and the novel antidepressant, tianeptine (2.5-10.0 mg/kg), on the behaviour of mice in the elevated plus-maze test of anxiety. Compounds were administered daily for 21 days prior to testing, and an ethological scoring technique was used to generate comprehensive behavioural profiles. Results show that subchronic treatment with ondansetron failed to influence the behaviour of mice in the plus-maze, while the limited changes induced by buspirone could not be attributed to anxiety-related processes. In contrast, tianeptine produced unambiguous anxiogenic-like effects at the top dose tested (10.0 mg/kg), a profile that was not secondary to changes in general levels of locomotor activity or exploration. Data are discussed in relation to current pharmacotherapy of anxiety and depressive disorders, and the nature of anxiety induced by animal models.

Animals↗

PubMed1997

Risk assessment behaviour: evaluation of utility in the study of 5-HT-related drugs in the rat elevated plus-maze test.

The present study compared the effects of a wide range of 5-hydroxytryptamine (5-HT)-modulating and potential anxiolytic agents in the rat elevated plus-maze using spatiotemporal (i.e., open arm time and entries) and ethologically derived measures (i.e., risk assessment activities and directed exploration). The drugs used were 5-HT1A receptor partial (buspirone and ipsapirone) and full (8-OH-DPAT and flesinoxan) agonists, mixed 5-HT2A/2C receptor antagonists (ritanserin, ketanserin, mianserin, and pirenperone), selective 5-HT3 receptor antagonists (ICS 205-930, MDL 72222, ondansetron, and (RS)-zacopride), and selective (fluoxetine, fluvoxamine, and zimelidine) and nonselective (imipramine) 5-HT reuptake inhibitors. Only buspirone and mianserin produced effects indicative of an anxiolytic-like action on the spatiotemporal measures. However, all 5-HT1A receptor ligands, as well as mianserin, ketanserin, ondansetron, and zacopride, decreased the number of aborted attempts at entry into open arms (risk assessment). In addition, buspirone, mianserin, and zacopride increased head-dipping (directed exploration). Among the 5-HT reuptake inhibitors, zimelidine reduced head-dipping and total entries. The present findings demonstrate that risk assessment responses are sensitive to the action of 5-HT1A receptor ligands, but their modulation by drugs targetting 5-HT2A, 5-HT2C, and 5-HT3 receptors was not convincingly established.

Animals↗

PubMed1997

Influence of 5-HT1A receptor antagonism on plus-maze behaviour in mice. II. WAY 100635, SDZ 216-525 and NAN-190.

To understand further the role of 5-hydroxytryptamine receptor subtype 1A (5-HT1A) mechanisms in anxiety, the behavioural effects of 5-HT1A receptor antagonists with different selectivity and intrinsic activity were examined using an ethological version of the murine elevated plus-maze test. WAY 100635 (0.03-9.0 mg/kg) produced a behavioural profile indicative of an anxiolyticlike effect, with an apparent bell-shaped dose-response relationship and increases in nonexploratory behaviours at the largest dose tested. SDZ 216-525 exerted a dose-dependent antianxiety action at doses of 0.05-0.8 mg/kg, with some loss of activity at 3.2 mg/kg. In contrast, smaller doses of NAN-190 had a significant effect, whereas higher doses (2.5-10.0 mg/kg) decreased locomotor activity and other active behaviours, a profile similar to that produced by the alpha1-adrenoceptor antagonist prazosin (2.5 mg/kg), which also inhibited open arm activity. Findings are discussed in relation to 5-HT1A receptor and alpha1-adrenoceptor antagonism and corresponding neurochemical changes. The results of the present series support the view that 5-HT1A receptor antagonists have therapeutic potential in the management of anxiety.

Animals↗

PubMed1997

Influence of 5-HT1A receptor antagonism on plus-maze behaviour in mice. I. Pindolol enantiomers and pindobind 5-HT1A.

Studies on the behavioural effects of 5-hydroxytryptamine receptor subtype 1A (5-HT1A) antagonists may provide important clues to the precise role of 5-HT1A receptor mechanisms in anxiety. In the first of a series of experiments designed to address this issue, the effects of mixed 5-HT1A and beta-adrenergic receptor antagonists pindolol enantiomers and pindobind 5-HT1A and of metoprolol and ICI 118,551 (selective beta1- and beta2-adrenoceptor antagonists, respectively) were assessed in the mouse elevated plus-maze using ethological techniques. Results showed that, at lower doses, (-)pindolol (0.1-1.6 mg/kg) and pindobind 5-HT1A (0.1-0.5 mg/kg) produced changes in both conventional and ethological measures (increased percentage of open arm time and reduced risk assessment) indicative of anxiety reduction. However, these anxiolyticlike actions were less evident at higher doses. In contrast, (+)pindolol (0.1-6.4 mg/kg), metoprolol (2.0-18.0 mg/kg) and ICI 118,551 (1.0-9.0 mg/kg) were behaviourally inert under present test conditions. These data suggest that antagonist actions at 5-HT1A receptors (but not beta-adrenoceptors) are involved in the anxiolyticlike effects of (-)pindolol and pindobind 5-HT1A in the murine elevated plus-maze test.

Adrenergic beta-Antagonists↗

PubMed1997

Anxiety, defence and the elevated plus-maze.

The elevated plus-maze test has been in use as a rodent model of anxiety for a decade, and is representative of those tests that are based upon the study of spontaneous behaviour patterns and which have high ecological validity. The origins of the test in studies of the relationship between exploration and fear are reviewed, and attention is drawn to the distinct possibility that variation in the pharmacosensitivity of the procedure may be attributable to often extreme methodological variation between laboratories. In considering further this issue, attention is also drawn to the need to collect data under constant test conditions and to provide the minimum database necessary to reach conclusions regarding the behavioural specificity of drug action. Recent research, which has extended the conventional plus-maze scoring technique to include specific behavioural acts and postures (in particular, those relating to defensive behaviour), is described. The value of such an ethological approach to the plus-maze is then exemplified with original data that demonstrate behaviourally selective, anti-anxiety effects of the GABAA receptor agonist, muscimol (0.125-1.0 mg/kg). It is concluded that, when used appropriately, the elevated plus-maze test can be a very valuable tool in drug screening and in the study of the neurobiology of anxiety and defence. More attention to behaviour and somewhat less emphasis on test simplicity and convenience would seem to be warranted.

Aggression↗

PubMed1997

Resistance of experientially-induced changes in murine plus-maze behaviour to altered retest conditions.

Prior exposure to the elevated plus-maze results in profound behavioural alterations in rats and mice, with 24 h retest profiles indicative of fear sensitization. The present study was designed to examine the influence of retest cues on this phenomenon in male DBA/2 mice. Results confirmed the potent influence of prior maze experience on subsequent behavioural patterns, and showed that this was not affected by manipulations of extra-maze cues (90 degrees re-orientation of the maze or use of a different laboratory) on Trial 2. Data are discussed in relation to experientially-induced shifts in behavioural strategy and the apparent involvement of simple proximal cues (probably thigmotactic) in this enduring and adaptive form of spatial learning.

Animals↗

PubMed1997

Animal models of 'anxiety': where next?

Numerous procedures have been developed to facilitate preclinical research on the behavioural pharmacology of anxiety and, as a result of this application, are often referred to as animal models of 'anxiety'. This is an unfortunate misnomer, not only because of the apparent inability of many tests to detect novel anxiolytics consistently, but also because the term implies that anxiety is a unitary emotion. Such difficulties have arisen largely as a consequence of test development strategies which, by emphasizing pharmacological (i.e. benzodiazepine) validation, have yielded models predictive of a specific type of anxiolytic activity. The present review argues that the refinement of existing tests as well as the development of new procedures requires urgent attention to the much neglected issue of behavioural validation. From an evolutionary perspective, normal human anxiety may be conceptualized as a repertoire of defence reactions tailored to meet different forms of threats, and disorders of anxiety as the inappropriate activation or exaggeration of these usually adaptive response patterns. In this context, consideration of the defensive reactions typically observed in our animal models reveals substantially greater commonality in the behavioural effects of benzodiazepine and 5-HT1A anxiolytics than would otherwise be apparent. Therefore, with the exception of the conventional plus-maze paradigm (discussed at some length), better correspondence is seen in tests involving unconditioned response to potential threat (e.g. social interaction, distress vocalizations and light/dark exploration) than in tests of conditioned fear reactions. Even within the latter grouping, however, greater commonality is seen in procedures based on reactions to proximal threat (e.g. freezing, startle, ultrasonic vocalizations, burying) than those involving reactions to distal threat (e.g. avoidance/flight). Significantly, very similar findings have been reported in tests specifically designed to study defensive reactions (e.g. rat and mouse defence test batteries) or which incorporate a more detailed knowledge of defence into established procedures (e.g. ethological plus-maze and defensive burying paradigms). Furthermore, recent evidence also suggests that drugs with proved clinical efficacy in panic attacks/panic disorder have reliably stronger effects on flight responses than other components of the defensive repertoire. It is concluded that a focus on defensive behaviour patterns improves test validity (predictive/face/construct), offers a more rational basis for test selection in drug development programmes, and provides a firmer theoretical framework for future methodological and therapeutic advance.

Animals↗

PubMed1997

Animal models of anxiety: an ethological perspective.

In the field of anxiety research, animal models are used as screening tools in the search for compounds with therapeutic potential and as simulations for research on mechanism underlying emotional behaviour. However, a solely pharmacological approach to the validation of such tests has resulted in distinct problems with their applicability to systems other than those involving the benzodiazepine/GABAA receptor complex. In this context, recent developments in our understanding of mammalian defensive behaviour have not only prompted the development of new models but also attempts to refine existing ones. The present review focuses on the application of ethological techniques to one of the most widely used animal models of anxiety, the elevated plus-maze paradigm. This fresh approach to an established test has revealed a hitherto unrecognized multidimensionality to plus-maze behaviour and, as it yields comprehensive behavioural profiles, has many advantages over conventional methodology. This assertion is supported by reference to recent work on the effects of diverse manipulations including psychosocial stress, benzodiazepines, GABA receptor ligands, neurosteroids, 5-HT1A receptor ligands, and panicolytic/panicogenic agents. On the basis of this review, it is suggested that other models of anxiety may well benefit from greater attention to behavioural detail.

Animals↗

PubMed1996

Ethological analysis of cholecystokinin (CCKA and CCKB) receptor ligands in the elevated plus-maze test of anxiety in mice.

The literature on the effects of CCK receptor manipulations in animal models of anxiety is rife with inconsistency, and the data subject to a variety of methodological and interpretative difficulties. In the present paper, the effects of a range of CCK receptor ligands on anxiety in male mice have been assessed using an ethological version of the elevated plus-maze test. Compounds selected for study were the agonists, CCK-4 and CCK-8s (12.5-100 micrograms/kg), and the antagonists, devazepide, L-365, 260 and PD 135158 (1.0 microgram/kg-1.0 mg/kg). CCK-4 failed to produce any significant behavioural effects over the dose range tested, while treatment with the sulphated octapeptide, CCK-8s, induced signs of behavioural inhibition at 100 microgram/kg without altering anxiety-related indices. Furthermore, in contrast to the clear anxiolytic profile of diazepam (1 mg/kg), and despite the comprehensive behavioural profiles yielded by ethological analysis, all three CCK receptor antagonists studied (devazepide, L-365, 260 and PD 135158) were found to be without significant effect under present test conditions. Together, present findings provide little support for the involvement of CCK receptor mechanisms in anxiety and, in particular, the form of anxiety evoked in mice by exposure to a plus-maze.

Animals↗

PubMed1996

GABAergic influences on plus-maze behaviour in mice.

Manipulations of GABA function have been found to produce highly variable effects in animal models of anxiety. In the present series, an ethological version of the murine elevated plus-maze was used to examine in detail the behavioural profiles of diazepam (1.5 mg/kg; positive control) and a range of GABA-related compounds: valproic acid (100-400 mg/kg), No-711 (1.25-10.0 mg/kg), muscimol (0.5-3.0 mg/kg), (+)bicuculline (4.0-8.0 mg/kg), picrotoxin (0.25-2.0 mg/kg), R(+)baclofen (0.375-3.0 mg/kg) and CGP 35348 (25-200 mg/kg). On both conventional and ethological indices, results confirmed the anxiolytic profile of diazepam under present test conditions, and revealed substantially similar effects for the GABA-T inhibitor, valproic acid (100-400 mg/kg), and the GABAA receptor agonist, muscimol (2 mg/kg). The GABA reuptake inhibitor, No-711, produced weak anxiolytic-like effects at low doses (1.25-2.5 mg/kg) but disrupted behaviour at the highest dose tested (10 mg/ kg). Although the GABAA receptor antagonists, (+)bicuculline and picrotoxin, produced changes indicative of anxiety enhancement, concomitant behavioural suppression was evident at high doses (8 mg/kg and 1-2 mg/kg, respectively). Further studies suggested that the effects observed with bicuculline may be mediated by an active metabolite, such as bicucine. In contrast to the effects of valproic acid and direct GABAA receptor manipulations, the GABAB receptor agonist, R(+) baclofen, non-specifically disrupted behaviour at the highest dose tested (3 mg/kg) while the GABAB receptor antagonist, CGP 35348, was inactive over the dose range studied. Although present data confirm the sensitivity of the plus-maze to agents which modify GABAA receptor function, further studies will be required in order more fully to characterize this relationship.

Animals↗

PubMed1996

Effects of chlordiazepoxide on maternal aggression in mice depend on experience of resident and sex of intruder.

Lactating mice respond differentially to intruders of differing sex, displaying defensive attack against the male and offensive attack against the female. Such a phenotypic dichotomy appears to have adaptive value in that unfamiliar males pose a much greater threat to the offspring than do females. The present study examined the effects of the benzodiazepine anxiolytic chlordiazepoxide (CDP) (2.5-10.0 mg/kg) on this differential response pattern in aggression-naive (nonscreened) (NS) and aggression-experienced (screened) (S) lactating female mice (Mus musculus domesticus) confronting intruders of either sex in a 10-min test. This procedure was used to evaluate the influence of both the type of opponent and previous aggressive experience on basal behavioural profiles and drug action. Results showed that both intruder sex and prior screening for attack modulated the behaviour of lactating females toward intruders. In turn, both variables strongly influenced CDP effects on maternal aggression. In particular, in S dams, CDP dose-dependently increased maternal attack against males but decreased attack against female intruders. Conversely, in NS dams, CDP decreased attack (and fear) against males but did not affect it against females. In both S and NS conditions, CDP modified the attack strategy of lactating females against the male, switching it from a defensive to an offensive pattern. Exploration, social investigation, eating, and immobility were differentially affected by the drug treatment, depending on screening and/or intruder sex condition. These differential effects of CDP between S and NS conditions, toward either male or female intruders, cannot be fully explained by differences in the baseline levels of these behaviours. Alternative hypotheses are discussed. These findings demonstrate that the effects of CDP on maternal attack behaviour depend on not only the drug but also the object of attack, and hence the function of attack and the prior experience of the attacker.

Aggression↗

PubMed1996

Modulation of plus-maze behaviour in mice by the preferential D3-receptor agonist 7-OH-DPAT.

Differences in the behavioural profiles of dopamine D2 receptor antagonists (e.g., haloperidol vs. sulpiride) in a animal models of anxiety have prompted speculation concerning the importance of their relative affinities for D2-like receptor populations. In an initial attempt to investigate the involvement of D3 receptors in anxiety, the present study examined the effects of the preferential D3-receptor agonist, (+/-)7-OH-DPAT (0.01-10.0 mg/kg), on behaviours displayed by male mice in the elevated plus-maze paradigm. An ethological approach incorporating measurement of a range of defensive acts and postures in addition to conventional parameters was used to provide a comprehensive behavioural profile for the compound. Data analysis indicated a significant increase in percentage of open-arm entries at 10 mg/kg and an altered temporal distribution of behaviour at 1-10 mg/kg. Furthermore, risk-assessment measures (stretched attend postures, closed-arm returns) were dose dependently reduced by drug treatment. Although these behavioural changes would be consistent with anxiety reduction, such an interpretation is negated by dose-dependent decreases in all active behaviours (arm entries, rearing, and head-dipping) and by marked increases in entry latencies and nonexploratory behaviour at the highest dose tested. Overall, these effects are remarkably similar to those previously reported for quinpirole, suggesting either that D2 and D3 receptors exert similar behavioural control or that the agents employed are sufficiently potent at D2 receptors to prevent a resolution of D2 and D3 responses.

Animals↗

PubMed1996

Plus-maze retest profile in mice: importance of initial stages of trail 1 and response to post-trail cholinergic receptor blockade.

Recent research has shown that a single undrugged prior experience of the elevated plus-maze produces significant behavioural changes upon 24-h retest in rats and mice. Typically, when reexposed to the maze, animals display an increased avoidance of the open arms and a corresponding preference for the enclosed sections of the apparatus. Using ethological analyses, the present series of experiments sought to further characterize this phenomenon in mice and to determine whether or not it involves cholinergic receptor mechanisms. Results confirmed that behaviour during Trial 2 is markedly different to that seen on initial exposure, and that such changes are independent of the duration of Trial 1 (2 vs. 5 min). Retest behavioural changes included reduced entry latencies, reduced open arm entries, less time on the open arms and centre platform, lower levels of exploratory head-dipping, and increased entries into and time spent in the closed arms. The importance to the retest phenomenon of the first few minutes of initial exposure was further suggested by min-by-min analyses of the behaviour of animals naive to the maze. Results showed that behaviour during the first min is characterized by high levels of risk assessment from the centre platform and relatively low, but equal, levels of open- and closed-arm exploration. From min 2 onwards, however, behaviour showed a marked change with increasing open arm/centre platform avoidance, increasing closed-arm preference, and decreasing levels of risk assessment and exploratory head-dipping. Thus, it would appear that this within-session aversive learning transfers between sessions to account for behavioural profiles on retest. Irrespective of the duration of Trial 1 (2 or 5 min), posttrial administration of the muscarinic antagonist, scopolamine (0.1-1.0 mg/kg), failed to significantly alter the behavioural changes seen between trials. Data are discussed in relation to the apparent sensitization of fear produced by plus-maze exposure, its possible relation to phobia acquisition, and the need for further research on underlying mechanisms.

Animals↗