Anticonflict Effect Research Articles

The Effects of Oral Lavender Therapy on Wounding in Chimpanzees (Pan troglodytes).

Lavender administration in humans has been shown to promote calmness without the side effects often observed with benzodiazepines. Studies in both humans and rodents have found that ingestion of oral lavender capsules resulted in significantly decreased anxiety. Additionally, mice developed an anti-conflict effect and humans increased socially inclusive behaviors. Given the safety of oral lavender oil and the observed benefits, we administered daily lavender capsules to six chimpanzees who exhibited conflict-instigating behaviors in an effort to further decrease our already low levels of wounding. We compared the total number of wounds in 25 chimpanzees housed with the six lavender-treated chimpanzees in five different social groups (1) prior to administration of daily oral lavender capsules to (2) total wounds during daily oral lavender capsule treatment. We hypothesized that lavender therapy treatment would reduce overall wounding in the social groups. Surprisingly, overall wounding was higher during the lavender treatment period (p = 0.01), yet the percentage of wounds requiring treatment significantly decreased during the lavender therapy period (36% vs. 21%, p = 0.02).

8-Substituted Triazolobenzodiazepines: In Vitro and In Vivo Pharmacology in Relation to Structural Docking at the α1 Subunit-Containing GABAA Receptor.

In order to develop improved anxiolytic drugs, 8-substituted analogs of triazolam were synthesized in an effort to discover compounds with selectivity for α2/α3 subunit-containing GABAA subtypes. Two compounds in this series, XLi-JY-DMH (6-(2-chlorophenyl)-8-ethynyl-1-methyl-4H-benzo [f][1,2,4]triazolo[4,3-a][1,4]diazepine) and SH-TRI-108 [(E)-8-ethynyl-1-methyl-6-(pyridin-2-yl)-4H-benzo [f][1,2,4]triazolo[4,3-a][1,4]diazepine], were evaluated for in vitro and in vivo properties associated with GABAA subtype-selective ligands. In radioligand binding assays conducted in transfected HEK cells containing rat αXβ3γ2 subtypes (X = 1,2,3,5), no evidence of selectivity was obtained, although differences in potency relative to triazolam were observed overall (triazolam > XLi-JY-DMH > SH-TRI-108). In studies with rat αXβ3γ2 subtypes (X = 1,2,3,5) using patch-clamp electrophysiology, no differences in maximal potentiation of GABA-mediated Cl− current was obtained across subtypes for any compound. However, SH-TRI-108 demonstrated a 25-fold difference in functional potency between α1β3γ2 vs. α2β3γ2 subtypes. We evaluated the extent to which this potency difference translated into behavioral pharmacological differences in monkeys. In a rhesus monkey conflict model of anxiolytic-like effects, triazolam, XLi-JY-DMH, and SH-TR-108 increased rates of responding attenuated by shock (anti-conflict effect) but also attenuated non-suppressed responding. In a squirrel monkey observation procedure, both analogs engendered a profile of sedative-motor effects similar to that reported previously for triazolam. In molecular docking studies, we found that the interactions of the 8-ethynyl triazolobenzodiazepines with the C-loop of the α1GABAA site was stronger than that of imidazodiazepines XHe-II-053 and HZ-166, which may account for the non-sedating yet anxiolytic profile of these latter compounds when evaluated in previous studies.

Basolateral amygdalar inactivation blocks chronic stress-induced lamina-specific reduction in prefrontal cortex volume and associated anxiety-like behavior

Chronic exposure to stress causes cognitive deficits, anxiety and depression. Earlier studies have suggested that the prefrontal cortex (PFC) and basolateral amygdala (BLA) can differentially modulate the stress-induced alterations either by their action on HPA axis or via direct reciprocal connections between them. The PFC dysfunction and BLA hypertrophy following stress are known to cause anxiety and affective symptoms. Recent studies indicate that inactivation of BLA projections to PFC remarkably decreases anxiety. However, the effect of BLA inactivation on stress-induced anxiety and associated volume loss in prelimbic (PrL) and anterior cingulate (ACC) subregions of PFC is not known. Accordingly, we evaluated the effect of BLA lesion or inactivation during chronic immobilization stress (CIS) on an approach-avoidance task and associated volume loss in the PFC. The stressed rats showed a significant volumetric reduction in layer I and II of the PrL and ACC. Interestingly, BLA lesion prior to stress prevented the volume loss in PrL and ACC. Further, BLA lesion blocked the anxiety-like behavior in stressed rats. However, in the absence of stress, BLA lesion increased the number of shocks as compared to controls. As BLA lesion produced an anticonflict effect, we performed temporary inactivation of BLA specifically during stress. Similar to BLA lesion, lidocaine-induced inactivation prevented the stress-induced volume loss and anxiety-like behavior. We demonstrate that inactivation of BLA during stress prevents CIS-induced anxiety and associated structural correlates in the PFC. The present study extends the hypothesis of amygdalar silencing as a possible management strategy for stress and associated disorders.

The Roman high- and low-avoidance rats differ in the sensitivity to shock-induced suppression of drinking and to the anxiogenic effect of pentylenetetrazole

The Roman high- (RHA) and low-avoidance (RLA) outbred rat lines are selected for respectively rapid vs. poor acquisition of active avoidant behavior. Emotional reactivity appears to be the most prominent behavioral difference between the two lines, with RLA rats being more fearful/anxious than their RHA counterparts. Accordingly, here we show that shock-induced inhibition of drinking behavior in the Vogel's test is significantly more pronounced in RLA than RHA rats. Thus, unpunished drinking activity is similar in both lines (38.1 ± 0.9 and 36.4 ± 0.6 licking periods/3 min in RLA and RHA rats, respectively), whereas under punished conditions (0.05–1.00 mA electric shocks delivered through the drinking tube) a more robust decrease in drinking behavior is observed in RLA vs. RHA rats. Moreover, fear-related behaviors like freezing and self-grooming are more frequent in RLA than RHA rats throughout the test. Similar results are obtained with the inbred RHA-I and RLA-I rats, which have been selected and bred through brother/sister mating of the outbred lines. In keeping with the above findings, we also show that, compared with their RHA counterparts, the outbred RLA rats are similarly responsive to the anticonflict effect of diazepam but more responsive to the proconflict effect of pentylenetetrazole in the Vogel's test. Collectively, these results reveal another behavioral trait distinguishing RHA from RLA rats and add experimental support to the view that the Roman lines/strains are a valid genetic model for the study of the neural underpinnings of fear/anxiety- and stress-related behaviors.

DECREASED REACTIVITY TO ANXIOLYTICS CAUSED BY EARLY PROTEIN MALNUTRITION IN RATS

In order to investigate whether early malnutrition causes lasting changes in the reactivity to anxiolytic drugs, rat dams lactation (21 days) and pops after weaning until the 49th day of life were fed on 8% casein diet (M rats), while their well-nourished controls received 25% casein (W rats), from day 50 on all animals ate the same balanced diet. Experiments started on the 91st day. Rats deprived for 22 hours drank water containing either 1.8% or 2.7% sodium chloride for 30 min in a test chamber, total intake being measured. Dose-effect curves for diazepam (0.5-5.0 mg/kg, IP), as well as for the monbenzodiazepine anxiolytics ipsapirone (0.5-5.0 mg/kg), ritanserin (0.05-1.0 mg/kg) and isamoltane (2.5-20.0 mg/kg) were determined in M as well as in W rats. Diazepam and ipsapirone dose-dependently released drinking suppressed by either salt concentration in W rats, but caused little or no effect in M rats. Ritanserin and isamoltane were ineffective in both groups. These and previously reported results show that early protein malnutrition markedly reduces anticonflict effect of anxiolytics, indicating long-lasting impairment of neuronal systems underlying emotional behavior. Keywords: early protein malnutrition, hypertonic saline intake, diazepam, ipsapirone.

Role of α3GABAA receptor modulation in the anti-conflict effects of benzodiazepine-type drugs in monkeys

Role of α3GABAA receptor modulation in the anti-conflict effects of benzodiazepine-type drugs in monkeys

Self-reported collision involvement associated with driving after alcohol use, cannabis use or both

Self-reported collision involvement associated with driving after alcohol use, cannabis use or both

Use of naloxone in the treatment of benzodiazepine poisoning

We read with interest the recent article by Solhi et al., studying the use of naloxone in benzodiazepine poisoning treatment and the comments by Jang et al. It is an interesting topic and we would like to express our thoughts on these comments and concerns based on the literature review. Jang et al. had a concern: ‘Since naloxone is a known antidote for opioid toxicity, it is very important to exclude their presence to validate the data obtained’. This is a good point to make this article better. However, this might not affect the final conclusion in this study based on the results. First, a number of studies show that the prevalence of current benzodiazepine use in methadone-maintenance treatment populations varies between 24.9% and 50.6%. However, prevalence data suggest that most benzodiazepine users do not take illegal drugs. In the study by Solhi et al., after a naloxone injection, 80%–100% of the patients, varying by type of benzodiazepine, significantly improved the main signs and symptoms such as lethargy, weakness, and ataxia, while there was no improvement in the control groups. It is unlikely that 80%–100% of the patients in this study were using illegal drug or synthetic opioids. In another word, there must be few, if not all, patients without any illegal drug or synthetic opioid use, whose symptoms and clinical signs were improved by naloxone, but not by control treatments. Second, animal studies provide direct evidence that naloxone antagonizes gamma-aminobutyric acid (GABA)/benzodiazepine receptor functions. Electrophysiological data show that GABA-induced inhibition of neuronal firing in the brain of rat can be antagonized by naloxone. Furthermore, in experimental animals, naloxone antagonizes various benzodiazepine-induced behaviors, for example, hyperdipsia, hyperphagia, anticonflict effects, and anxiolytic-like effects. These data suggest the direct interaction of naloxone with GABA/benzodiazepine receptor functions. In summary, this study provides useful information on the treatment of benzodiazepine poisoning by naloxone. The nature of the mechanism involved, which needs further study, might involve its interaction with GABA receptors.

Kindling of the lateral septum and the amygdala: Effects on anxiety in rats

Long-term kindling of limbic system structures may produce substantial changes in emotional behavior in rats. This study examined long-term changes in two kindled structures that have opposite effects on anxiety, the lateral septum and the central nucleus of the amygdala. The purpose of the experiment was to examine the specificity of the emotional effects of kindling by employing a double dissociation design. Animals were tested in two common animal models of anxiety, the water-lick conflict test and the elevated plus-maze. In the conflict test amygdala-kindled animals demonstrated a significant anxiolytic effect when compared with sham-kindled animals. This effect was potentiated by chlordiazepoxide. Septally-kindled animals exhibited a significant anticonflict effect when compared to sham-kindled animals in the first session. Septally-kindled animals spent significantly more time on the open arms of the elevated plus-maze than did sham-kindled animals. Observed changes persisted 6weeks after the termination of 150 kindling sessions. The effects of long-term kindling were highly consistent with those of disruption rather than facilitation.

Stimulation of postsynaptic 5-HT1A receptors is responsible for the anticonflict effect of ipsapirone in rats.

Ipsapirone (1.25-10 mg kg-1), a non-benzodiazepine anxiolytic drug with high affinity for 5-hydroxytryptamine1A (5-HT1A) receptors, increased dose-dependently the number of punished licks in the drinking conflict test (Vogel test) in rats. The anticonflict effect of the drug administered at a dose of 5 mg kg-1 was not modified in animals with lesions of 5-HT neurones, produced by p-chloroamphetamine (PCA, 2 x 10 mg kg-1). The anticonflict effect of ipsapirone in PCA-pretreated rats was antagonized by the 5-HT1A receptor and alpha 1-adrenoceptor antagonist NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-phthalimmido)]butylpiperazine hydrobromide; 0.5-1 mg kg-1), but not by the selective alpha 1-adrenoceptor blocker prazosin (0.5 mg kg-1). Neither NAN-190 nor prazosin affected the punished response in PCA-pretreated rats. The present results indicate that the anticonflict effect of ipsapirone depends on stimulation of postsynaptic 5-HT1A receptors.

Anticonflict and reinforcing effects of triazolam + pregnanolone combinations in rhesus monkeys.

Combinations of positive modulators of benzodiazepine and neuroactive steroid sites on GABA(A) receptors have been shown to act in an additive or supra-additive manner depending on the endpoint under study, but they have not been assessed on experimentally induced conflict or drug self-administration. The present study examined the interactive effects of the benzodiazepine triazolam and the neuroactive steroid pregnanolone in a rhesus monkey conflict procedure (a model of anxiolysis) and on a progressive-ratio schedule of drug self-administration (a model of abuse potential). Both triazolam and pregnanolone decreased rates of nonsuppressed responding, whereas only triazolam consistently increased rates of suppressed responding (i.e., had an anticonflict effect). Fixed-ratio mixtures of triazolam and pregnanolone also decreased rates of nonsuppressed responding and did so in an additive manner. In contrast, mixtures of triazolam and pregnanolone produced either additive or supra-additive rate-increasing effects on suppressed responding, depending on the proportion of drugs in the mixture. Both triazolam and pregnanolone were self-administered significantly, and triazolam and pregnanolone mixtures had either proportion-dependent additive or infra-additive reinforcing effects. These results suggest that combinations of triazolam and pregnanolone may have enhanced anxiolytic effects with reduced behavioral disruption and abuse potential compared with either drug alone.

Contribution of GABA(A) receptors containing α3 subunits to the therapeutic-related and side effects of benzodiazepine-type drugs in monkeys.

Experimental evidence suggests that the differential behavioral effects of benzodiazepines depend on their relative actions at γ-aminobutyric acid type A (GABA(A)) receptors that contain either an α1, α2, α3, or α5 subunit. The present study was aimed at understanding the role of α3 subunit-containing GABA(A) (α3GABA(A)) receptors by examining the behavioral pharmacology of TP003 (4,2'-difluoro-5'-[8-fluoro-7-(1-hydroxy-1-methylethyl)imidazo[1,2-a]pyridine-3-yl]biphenyl-2-carbonitrile), which shows functional selectivity for α3GABA(A) receptors. First, a conflict procedure was used to assess the anxiolytic-like effects of TP003 and a representative clinically available benzodiazepine. TP003 was also administered before daily periods of sucrose pellet availability to evaluate potential hyperphagic effects. In separate experiments, observable behavioral effects were used to assess the motor and sedative effects of TP003. Administration of TP003 produced robust anti-conflict effects without the rate-decreasing effects that were observed with the representative benzodiazepine. Unlike the reported effects of benzodiazepines, TP003 did not enhance palatable food consumption. However, increases in observable sleep-associated posture were induced by TP003, as were decreases in some species-typical behaviors (vocalization, locomotion, and environment-directed behaviors). When evaluated for its ability to induce a procumbent posture, TP003 failed to produce an effect. Based on conflict and observation tests in monkeys, our results suggest that TP003 may have anxiolytic properties but lack ataxic, hyperphagic, and pronounced sedative effects characteristic of classical benzodiazepines. TP003 did induce myorelaxant-like effects and had relatively mild sedative effects. Collectively, these results suggest that α3GABA(A) receptors play an important role in the anxiolytic-like and motor effects of benzodiazepine-type drugs.

Emergence of anti-conflict effects of zolpidem in rhesus monkeys following extended post-injection intervals.

Zolpidem is a hypnotic drug that binds to γ-aminobutyric acid type A receptors but lacks consistently demonstrable anxiolytic efficacy. Rhesus monkeys (N = 4) were trained under a multiple schedule in which food-maintained responding was programmed (18-response fixed ratio) for a 5-min period, followed by a 5-min period in which the food-maintained responding was suppressed by response-contingent electric shock (20-response fixed ratio). Doses of zolpidem (range = 0.03 to 1.0mg/kg, i.v.) were administered 5min before the session, and responding was re-assessed at three additional 20-min intervals. A similar experiment also was carried out with the non-selective benzodiazepine, triazolam, over a dose range of 0.001 to 0.1mg/kg, i.v. Zolpidem did not engender a significant increase in average rates of suppressed responding at earlier time points; however, rates of non-suppressed responding were robustly decreased. At 45- and 65-min post-injection, zolpidem treatment resulted in a dose-dependent increase in rates of suppressed responding. In contrast, the non-selective benzodiazepine triazolam increased rates of suppressed responding in a dose-dependent manner at all four time points, although decreases in non-suppressed responding were less at the later time points. These findings suggest that zolpidem has anxiolytic-like effects, but only >25min after i.v. injection in this rhesus monkey conflict model. It was hypothesized that time-dependent effects on the response rate-suppressing properties of zolpidem become tolerant (i.e., acute tolerance). Because anxiolytic-like effects remain stable throughout the session, the absence of rate-decreasing effects may "unmask" anti-conflict effects.

Antibodies to S100 proteins have anxiolytic-like activity at ultra-low doses in the adult rat

S100 proteins are small calcium-binding proteins interacting with numerous intra- and extra cellular targets involved in diverse physiological functions. In particular, S100 proteins may be involved in the regulation of anxiety-related behaviour. In the present study, the effects of affinity-purified antibodies to S100 proteins administered orally at ultra-low doses were evaluated in pre-clinical tests for anxiolytic-like activity in the adult rat. In the Vogel conflict test in the rat, antibodies to S100 proteins increased punished drinking (anti-conflict effect) at 5 and 7.5 mL kg(-1), but not at 2.5 or 10 mL kg(-1). Antibodies to S100 proteins increased the percentage of entries into the open arms of an elevated plus-maze at 10 mL kg(-1), but not at lower doses. Taken together, these results indicate the presence of anxiolytic-like activity for antibodies to S100 proteins over the dose range 5-10 mL kg(-1) in the adult rat.

The peeping response of pigeons (Columba livia) to isolation from conspecifics and exposure to a novel environment

The present study examined the acute behavioral responses of pigeons to separation from conspecifics and exposure to an unfamiliar environment (UE). The effects of (1) repeated exposure to the UE; (2) visual isolation from surroundings, or saline injections; and (3) diazepam treatment (i.p., 0.25, 0.75, 2.5 or 7.5mg/kg) before the trial were also examined. UE exposure evoked intense ballistic head movements (peeping), gradually replaced with angular head movements (AHM), both associated with immobility of the trunk and legs. These behaviors failed to habituate after three trials (7-day intertrial intervals). Visual isolation from the surroundings and saline injection prior to exposure to the UE increased the AHM and reduced peeping. Doses of diazepam (0.25 and 0.75 mg/kg) that have demonstrated anti-conflict effects in other tests did not affect the behavioral responses to the UE. Diazepam at 2.5 and 7.5mg/kg doses consistently increased time spent in immobility. These data suggest that peeping, although expressed in potentially threatening or harmful situations appears not to be a fear-motivated behavior or, alternatively, this specific behavioral response is not diazepam sensitive.

The anxiolytic-like effect of the selective 5-HT6 receptor antagonist SB-399885: The impact of benzodiazepine receptors

The effect of lesion of 5-hydroxytryptamine (5-HT) neurons, produced by p-chloroamphetamine (p-CA; 2×10 mg/kg), and the influence of the benzodiazepine receptor antagonist flumazenil (10 mg/kg) on the anticonflict action of N-[3,5-dichloro-2-(methoxy)phenyl]-4-(methoxy)-3-(1-piperazinyl)benzenesulfonamide (SB-399885), a selective 5-HT6 receptor antagonist, were investigated in the Vogel conflict drinking test in rats. In addition, the interaction between SB-399885 (0.3 mg/kg) and diazepam (2.5 mg/kg) was evaluated in that test. All the compounds tested were administered intraperitoneally. The anticonflict activity produced by SB-399885 (3 mg/kg) was not modified in p-CA-pretreated rats, but it was totally blocked by flumazenil. Combined administration of non-active doses of SB-399885 (0.3 mg/kg) and diazepam (2.5 mg/kg) produced a pronounced anticonflict effect in rats. The present results suggest that the anticonflict activity of SB-399885 is not conditioned by the integrity of 5-HT neurons, and that benzodiazepine receptors are indirectly involved in its effect, possibly due to a functional interaction between 5-HT6 receptors and the γ-aminobutyric acid (GABA)/benzodiazepine system.

Anxiolytic-like and antidepressant-like effects produced by the selective 5-HT6 receptor antagonist SB-258585 after intrahippocampal administration to rats

The purpose of this study was to investigate the effect of SB-258585, a selective 5-HT6 receptor antagonist, administered intrahippocampally to rats, in the conflict drinking and forced swim tests, that is models used for evaluating anxiolytic-like and antidepressant-like activity, respectively. Diazepam and imipramine were used as reference drugs. SB-258585 at a dose of 1 microg (but not 0.3 and 3 microg) showed an anticonflict effect that was weaker than that of diazepam (40 microg). SB-258585 at a dose of 3 microg (but not 1 and 10 microg) produced a marked anti-immobility effect comparable with that of imipramine (0.1 microg). The anxiolytic-like and antidepressant-like activity of SB-258585 seemed to be specific, as that compound--when given by the same route in doses effective in each model--did not affect the shock threshold, nonpunished water consumption, or exploratory activity of rats. The results obtained indicate that the hippocampus is one of the neuroanatomical sites involved in the anxiolytic-like and antidepressant-like activity of the selective 5-HT6 receptor antagonist SB-258585.

Anxiolytic-like effects induced by medial prefrontal cortex inhibition in rats submitted to the Vogel conflict test

Conflicting results have been obtained in studies aimed at investigating the role of the ventral portion of the medial prefrontal cortex (vMPFC), which comprise the prelimbic cortex (PL) and infralimbic cortex (IL), on anxiety responses in rodents evoked by animal models such as fear conditioning, elevated plus maze or social interaction. This may reflect the use of different lesion techniques and/or experimental paradigms based on distinct behaviors properties. Among the latter, the Vogel punished-licking test has been widely used to measure anxiety. However, the role of the vMPFC on anxiety-like behavior evoked by the Vogel model has not been evaluated. Thus, the present study verified the effects of acute and reversible bilateral inhibition of the vMPFC on the behavioral responses in the Vogel conflict test. After 24 h of water deprivation, male Wistar rats were subjected to an initial 3-min non-punished (pretest) drinking session. After an additional 24-h period of water deprivation they were exposed to a 3-min punished-licking session (test).Bilateral microinjections of lidocaine 2% (200 nL) or CoCl 2 (1 mM/200 nL) into the PL or IL produced similar anticonflict effects, increasing the number of punished licks. No responses were observed when lidocaine 2% was microinjected into vMPFC surrounding structures such as the cingulate cortex area 1, the corpus callosum and the tenia tecta. In control experiments the drugs did not change the number of unpunished licks nor had any effect in the tail-flick test. The present results, therefore, indicate that the vMPFC is involved in the behavioral responses elicited by punished stimuli.

Anticonflict effects of lavender oil and identification of its active constituents

The pharmacological effects of lavender oil were investigated using two conflict tests in ICR mice, and then the active constituents were identified. Lavender oil produced significant anticonflict effects at 800 and 1600 mg/kg in the Geller conflict test and at 800 mg/kg in the Vogel conflict test, suggesting that the oil has an anti-anxiety effect. Analysis using GC/MS revealed that lavender oil contains 26 constituents, among which α-pinene (ratio, 0.22%), camphene (0.06%), β-myrcene (5.33%), p-cymene (0.3%), limonene (1.06%), cineol (0.51%), linalool (26.12%), borneol (1.21%), terpinene-4-ol (4.64%), linalyl acetate (26.32%), geranyl acetate (2.14%) and caryophyllene (7.55%) were identified. We examined the effects of linalool, linalyl acetate, borneol, camphene, cineol, terpinen-4-ol, α-pinene and β-myrcene using the Geller and Vogel conflict tests in ICR mice. Cineol, terpinen-4-ol, α-pinene and β-myrcene did not produce any significant anticonflict effects in the Geller test. Linalyl acetate did not produce any significant anticonflict effects in either test. Both borneol and camphene at 800 mg/kg produced significant anticonflict effects in the Geller, but not in the Vogel conflict test. Linalool, a major constituent of lavender oil, produced significant anticonflict effects at 600 and 400 mg/kg in the Geller and Vogel tests, respectively, findings that were similar to those of lavender oil. Thus, we concluded that linalool is the major pharmacologically active constituent involved in the anti-anxiety effect of lavender oil.

Potential anxiolytic and antidepressant effects of the selective 5-HT 7 receptor antagonist SB 269970 after intrahippocampal administration to rats

Using conflict drinking and forced swimming tests in rats, we examined the anxiolytic- and the antidepressant-like activity, respectively, of (2 R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]-pyrrolidine (SB 269970), a selective 5-HT 7 receptor antagonist, after its intrahippocampal administration. SB 269970 at doses of 0.3, 1 and 3 μg showed an anticonflict effect which was weaker than that of diazepam (40 μg), whereas SB 269970 at doses of 3 and 10 μg had marked anti-immobility action comparable to that of imipramine (0.1 μg). Importantly, the anxiolytic- and antidepressant-like activity of SB 269970 seemed to be specific, since that agent − when given by the same route in doses effective in either model – affected neither the shock threshold, nor the non-punished water consumption, nor the exploratory activity of rats. The obtained results indicate that the hippocampus is one of the neuroanatomical structures involved in the potential anxiolytic and, in particular, antidepressant activity of SB 269970.