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1.
In previous research, the drug flumazenil has been categorized both as a pure benzodiazepine antagonist and as a benzodiazepine
partial agonist. The following studies used an elevated plus maze to test whether flumazenil would exert any antianxiety action
in rats. While chlordiazepoxide (3.0 mg/kg), ethanol (0.75 g/kg), and the atypical benzodiazepine zolpidem (1.0 mg/kg) all
significantly increased time spent on the open arms and percent open arm entries, flumazenil (1–10 mg/kg) alone did not produce
any anxiolytic effects on the maze. Withdrawal from chronic ethanol treatment led to a decrease in open arm time and percent
open arm entries. Flumazenil (3.0 mg/kg) blocked these changes, suggesting that the effects of flumazenil are at least partially
dependent upon the levels of stress or anxiety in the subjects. An anxiolytic action of flumazenil was not seen following
the central administration of the neuropeptide corticotropin-releasing factor (CRF), which reduced open arm time on the elevated
plus maze. These results support the hypothesis that the mechanism of action for flumazenil effects on the anxiety observed
during ethanol withdrawal involves antagonism of an endogenous benzodiazepine inverse agonist, rather than activity as a partial
agonist or blockade of CRF-mediated effects.
Received: 30 September 1996/Final version: 23 December 1996 相似文献
2.
Amanda A. BraunMatthew R. Skelton Charles V. Vorhees Michael T. Williams 《Pharmacology, biochemistry, and behavior》2011,97(3):406-415
The elevated plus and zero mazes (Plus and Zero, respectively) are used to assess behavior related to anxiety in rodents but direct comparisons of the two tests are lacking for rats. We compared the two methods in adult male Sprague-Dawley rats. Untreated rats in the Zero spent more time in open zones and exhibited more head dips than in the Plus whereas start latency and closed area entries were lower in the Zero than in the Plus. Diazepam (1 mg/kg) exposure increased time in the open in both mazes. Restraint (60 min prior to testing), yohimbine (2.5 mg/kg), and caffeine (100 mg/kg) had the opposite effect, significantly decreasing time spent in open zones in both mazes. No sexual dimorphism in behavior was seen in either maze in untreated rats. Although more open area time was evident in untreated animals in the Zero, after drug challenge both mazes detected anxiolytic and anxiogenic effects equally. Zero maze data can be analyzed directly because no center region exists; otherwise the two methods appear comparable following challenge. 相似文献
3.
RATIONALE: In rodents, a common response to many drugs of abuse, including ethanol (EtOH), is locomotor stimulation. It has been proposed, although debated, that EtOH-induced locomotor stimulation may represent an animal model of EtOH's euphoric effects. Another possibility is that this behavioral phenotype may represent an altered state of anxiety, and/or stress axis activation. OBJECTIVES: Mouse lines selectively bred for sensitivity (FAST) or resistance (SLOW) to EtOH's low dose locomotor stimulant effects were tested for differential sensitivity to EtOH's anxiolytic and/or stress axis activating effects, with the goal of detecting genetic correlations. METHODS: Saline- and EtOH-treated FAST and SLOW mice were tested on the elevated plus maze and the light-dark box, two widely used measures of anxiety-related behavior in rodents. In addition, serum corticosterone (CORT) levels were measured at various time points following injection of saline or ethanol. RESULTS: Behavioral data from both anxiety tests showed that FAST mice were less sensitive to EtOH's anxiolytic effects than were SLOW mice. Moreover, late recovery of elevated serum CORT levels following mild saline injection stress, as well as reduced CORT release in response to EtOH, suggested that FAST mice may possess a less responsive stress axis. CONCLUSIONS: These results provide evidence that sensitivity to the effects of EtOH on locomotor behavior, anxiety-like behavior, and the stress axis share some genetic influence. 相似文献
4.
Involvement of the opioid system in the effects induced by nicotine on anxiety-like behaviour in mice 总被引:3,自引:3,他引:0
Rationale Recent studies have revealed the participation of the endogenous opioid system in several behavioural responses induced by
nicotine including antinociception, rewarding properties, and physical drug dependence.
Objectives The present study was designed to examine the possible involvement of the various opioid receptors in the anxiolytic- and
anxiogenic-like responses induced by nicotine in mice.
Methods The acute administration of low (0.05) or high (0.8 mg/kg) doses of nicotine subcutaneously produced opposite effects in the
elevated plus maze, i.e. anxiolytic- and anxiogenic-like responses, respectively. Animals were only exposed once to nicotine.
The effects of the pretreatment with the μ-opioid receptor antagonist, β-funaltrexamine (5 mg/kg), the δ-opioid antagonist,
naltrindole (2.5 mg/kg) and the κ-opioid antagonist, nor-binaltorphimine (2.5 mg/kg) intraperitoneally were evaluated on the
anxiolytic- and anxiogenic-like responses induced by nicotine.
Results β-funaltrexamine, but not nor-binaltorphimine or naltrindole, abolished nicotine-induced anxiolytic-like effects, suggesting
an involvement of μ-opioid receptors in this behavioural response. On the other hand, naltrindole, but not nor-binaltorphimine
or β-funaltrexamine, increased the anxiogenic-like responses of nicotine, suggesting an involvement of δ-receptors in this
behavioural effect.
Conclusions These results demonstrate that the endogenous opioid system is involved in the effects induced by nicotine on anxiety-like
behaviour and provide new findings to further clarify the interaction between these two neurochemical systems. 相似文献
5.
Although cocaine is a powerful reinforcer, it has been reported to produce anxiety in humans and anxiogenic-like behavior
in animals. The goal of this study was three-fold: (1) to determine the doses of cocaine that induce anxiogenic-like behavior
in the elevated plus-maze in rats, (2) to determine if cocaine-associated contextual cues are capable of eliciting anxiogenic-like
behavior in the absence of the drug, and (3) to identify possible mechanisms through which cocaine-associated cues affect
behavior in the elevated plus-maze. Measurement of the amount of time that the animals spend exploring the open arms of the
maze provides a sensitive index of anxiogenic-like behavior in rats. In experiment 1, rats were injected with 10 mg/kg, 20 mg/kg,
or 30 mg/kg cocaine HCl or saline for 6 days. On day 6, the rats were tested in the elevated plus-maze 25 min after injection
with cocaine or saline. The animals chronically treated with the three doses of cocaine exhibited a dose-dependent increase
in anxiogenic-like behavior in the elevated plus-maze, compared to the saline-treated group. In experiment 2, cocaine-induced
(30 mg/kg) conditioning was achieved using a simple contextual design. On the final day of the experiment (day 6), after 5
days of conditioning, the rats were exposed for 25 min to the cocaine-associated contextual cues, then placed in the elevated
plus-maze. Animals that had been exposed to cocaine-associated contextual cues prior to being placed in the elevated plus-maze
exhibited a significant increase in anxiogenic-like behavior compared to the control groups. However, pretreatment of the
rats with the CRF antagonist, ∝-helical CRF9–41 (1 μg, ICV), on the test day, prior to exposure to cocaine-associated contextual cues, attenuated the subsequent anxiogenic-like
behavioral response in the elevated plus-maze (experiment 3). The results suggest that contextual cues associated with repeated
treatment with 30 mg/kg cocaine are capable of eliciting anxiogenic-like behavior in the absence of the drug and that CRF
mediates the expression of anxiogenic-like behaviors in the elevated plus-maze following exposure to cocaine-associated cues.
The conditioned anxiogenic action elicited by cocaine-associated cues may have relevance for understanding the complex addictive
nature of this drug and some of the clinical phenomena related to its use.
Received: 8 April 1997 / Final version: 18 December 1997 相似文献
6.
Hartley DE Edwards JE Spiller CE Alom N Tucci S Seth P Forsling ML File SE 《Psychopharmacology》2003,167(1):46-53
Rationale. Most commercial rodent diets are formulated with soya protein and therefore contain soya isoflavones. Isoflavones form one
of the main classes of phytoestrogens and have been found to exert both oestrogenic and anti-oestrogenic effects on the central
nervous system. The effects have not been limited to reproductive behaviour, but include effects on learning and anxiety and
actions on the hypothalamo-pituitary axis. It is therefore possible that the soya content of diet could have significant effects
on brain and behaviour and be an important source of between-laboratory variability.
Objectives. To determine whether behaviour in two animal tests of anxiety, and stress hormone production, would differ between rats that
were fed a diet which was free of soya isoflavones and other phytoestrogens (iso-free) and those that were fed a diet which
contained 150 μg/g of the isoflavones genistein and daidzein (iso-150). This controlled diet has an isoflavone concentration
similar to that in the maintenance diet routinely used in our institution.
Methods. Male rats were randomly allocated to the iso-free and iso-150 diets and their body weights and food and water consumption
were recorded for 14 days. They were then maintained on the same diets, but housed singly for 4 days, before testing in the
social interaction and elevated plus-maze tests of anxiety. Corticosterone concentrations in both dietary groups were determined
under basal conditions and after the stress of the two tests of anxiety. Vasopressin and oxytocin concentrations were determined
after brief handling stress.
Results. The groups did not differ in food or water intake, body weight or oxytocin concentrations. Compared with the rats fed the
iso-free diet, the rats fed the iso-150 diet spent significantly less time in active social interaction and made a significantly
lower percentage of entries onto the open arms of the plus-maze, indicating anxiogenic effects in both animal tests. The groups
did not differ in their basal corticosterone concentrations, but the iso-150 group had significantly elevated stress-induced
corticosterone concentrations. Stress-induced plasma vasopressin concentrations were also significantly elevated in the iso-150
diet group compared with the iso-free rats.
Conclusions. Major changes in behavioural measures of anxiety and in stress hormones can result from the soya isoflavone content of rat
diet. These changes are as striking as those seen following drug administration and could form an important source of variation
between laboratories.
Electronic Publication 相似文献
7.
Rationale An endocannabinoid signaling system has not been identified in hamsters.
Objective We examined the existence of an endocannabinoid signaling system in Syrian hamsters using neuroanatomical, biochemical, and
behavioral pharmacological approaches.
Materials and methods The distribution of cannabinoid receptors was mapped, and membrane fatty-acid amide hydrolase (FAAH) activity and levels of
fatty-acid amides were measured in hamster brain. The impact of cannabinoid CB1 receptor blockade and inhibition of FAAH was evaluated in the elevated plus maze, rota-rod test, and models of unconditioned
and conditioned social defeat.
Results A characteristic heterogeneous distribution of cannabinoid receptors was detected in hamster brain using [3H]CP55,940 binding and autoradiography. The FAAH inhibitor URB597 inhibited FAAH activity (IC50 = 12.8 nM) and elevated levels of fatty-acid amides (N-palmitoyl ethanolamine and N-oleoyl ethanolamine) in hamster brain. Anandamide levels were not reliably altered. The cannabinoid agonist WIN55,212-2 (1–
10 mg/kg i.p.) induced CB1-mediated motor ataxia. Blockade of CB1 with rimonabant (5 mg/kg i.p.) induced anxiogenic-like behavior in the elevated plus maze. URB597 (0.1–0.3 mg/kg i.p.) induced
CB1-mediated anxiolytic-like effects in the elevated plus maze, similar to the benzodiazepine diazepam (2 mg/kg i.p.). Diazepam
(2–6 mg/kg i.p.) suppressed the expression, but not the acquisition, of conditioned defeat. By contrast, neither URB597 (0.3–3.0 mg/kg
i.p.) nor rimonabant (5 mg/kg i.p.) altered unconditioned or conditioned social defeat or rota-rod performance.
Conclusions Endocannabinoids engage functional CB1 receptors in hamster brain to suppress anxiety-like behavior and undergo enzymatic hydrolysis catalyzed by FAAH. Our results
further suggest that neither unconditioned nor conditioned social defeat in the Syrian hamster is dependent upon cannabinoid
CB1 receptor activation. 相似文献
8.
《Biochemical pharmacology》2015,98(4):498-511
Anxiety disorders are a group of crippling mental diseases affecting millions of Americans with a 30% lifetime prevalence and costs associated with healthcare of $42.3 billion. While anxiety disorders show high levels of co-morbidity with smoking (45.3% vs. 22.5% in healthy individuals), they are also more common among the smoking population (22% vs. 11.1% in the non-smoking population). Moreover, there is clear evidence that smoking modulates symptom severity in patients with anxiety disorders. In order to better understand this relationship, several animal paradigms are used to model several key symptoms of anxiety disorders; these include fear conditioning and measures of anxiety. Studies clearly demonstrate that nicotine mediates acquisition and extinction of fear as well as anxiety through the modulation of specific subtypes of nicotinic acetylcholine receptors (nAChRs) in brain regions involved in emotion processing such as the hippocampus. However, the direction of nicotine’s effects on these behaviors is determined by several factors that include the length of administration, hippocampus-dependency of the fear learning task, and source of anxiety (novelty-driven vs. social anxiety). Overall, the studies reviewed here suggest that nicotine alters behaviors related to fear and anxiety and that nicotine contributes to the development, maintenance, and reoccurrence of anxiety disorders. 相似文献
9.
Daniele C. Aguiar Ana Luisa B. Terzian Francisco S. Guimarães Fabrício A. Moreira 《Psychopharmacology》2009,205(2):217-225
Rationale The endocannabinoid anandamide, in addition to activating cannabinoid type 1 receptors (CB1), may act as an agonist at transient
receptor potential vanilloid type 1 (TRPV1) channels. In the periaqueductal gray, CB1 activation inhibits, whereas TRPV1 increases,
anxiety-like behavior. In the medial prefrontal cortex (mPFC), another brain region related to defensive responses, CB1 activation
induces anxiolytic-like effects. However, a possible involvement of TRPV1 is still unclear.
Objectives In the present study, we tested the hypothesis that TRPV1 channel contributes to the modulation of anxiety-like behavior in
the mPFC.
Materials and methods Male Wistar rats (n = 5–7 per group) received microinjections of the TRPV1 antagonist capsazepine (1–60 nmol) in the ventral portion of the mPFC
and were exposed to the elevated plus maze (EPM) or to the Vogel conflict test.
Results Capsazepine increased exploration of open arms in the EPM as well as the number of punished licks in the Vogel conflict test,
suggesting anxiolytic-like effects. No changes in the number of entries into the enclosed arms were observed in the EPM, indicating
that there were no changes in motor activity. Moreover, capsazepine did not interfere with water consumption or nociceptive
threshold, discarding potential confounding factors for the Vogel conflict test.
Conclusions These data suggest that TRPV1 in the ventral mPFC tonically inhibits anxiety-like behavior. TRPV1 could facilitate defensive
responses opposing, therefore, the anxiolytic-like effects reported after local activation of CB1 receptors.
Daniele C. Aguiar and Ana Luisa B. Terzian contributed equally to this work. 相似文献
10.
Saitoh A Yamada M Yamada M Kobayashi S Hirose N Honda K Kamei J 《Psychopharmacology》2006,188(1):1-11
Rationale The role of Rho/Rho-associated kinase (ROCK) in regulating dendritic and axonal morphology during development has gained much attention. Very little is known, however, about the role of the Rho/ROCK pathway in emotional behavior.Objective To investigate the role of ROCK in emotional behaviors. We examined how the ROCK inhibitor Y27632 affects the performance of mice on three behavioral tests that measure anxiety-related behaviors.Results In the elevated plus-maze test, Y27632 (10 nmol, intracerebroventricular) induced a significant decrease in the percentage of time spent in the open arms and in the percentage of entries into open arms. In the fear conditioning test, Y27632-treated mice froze significantly more often and longer than did saline-treated mice. In the hole-board test, Y27632 significantly suppressed head-dipping behavior in Y27632-treated mice than in saline-treated mice. On the other hand, Y27632 did not produce on spontaneous alteration performance in the Y-maze test. These results indicate that ROCK inhibition increased anxiety-related behaviors.Conclusion Our findings suggest that the ROCK pathway is involved in the expression of anxiety- and fear-related behaviors. Furthermore, we propose that if the Rho/ROCK pathway plays an important role in mediating anxiety-related behaviors in humans, it may prove to be a novel system for anxiolytics to target. 相似文献
11.
The effect that chronic unpredictable stress had on the anxiety-like response elicited by the cannabinoid receptor agonist HU-210 [3-(1,1-dimethylheptyl)-(-)-11-hydroxy-delta 8-tetrahydrocannabinol] in the elevated plus maze was investigated here. Male Long-Evans rats were either unstressed or were subjected to a 21-day regimen of chronic unpredictable stress, and subsequently were subdivided into three testing groups (vehicle, 10 and 50 microg/kg of HU-210) and tested on the elevated plus maze. Results demonstrated that in unstressed animals, a low dose of HU-210 induced an anxiolytic response, whereas a high dose induced an anxiogenic response. Further, in stressed animals both the low and the high doses of HU-210 induced anxiogenic responses. These findings suggest that chronic stress enhances either cannabinoid receptor responsivity or one of the interacting systems implicated in emotional states. 相似文献
12.
Nguyen NK Keck ME Hetzenauer A Thoeringer CK Wurst W Deussing JM Holsboer F Müller MB Singewald N 《Psychopharmacology》2006,188(3):374-385
Rationale Regional-specific corticotropin-releasing factor receptor 1 (CRF-R1) knockout mice have been generated recently as a tool to dissociate CNS functions modulated by this receptor. In these mice, CRF-R1 function is postnatally inactivated in the anterior forebrain including limbic brain structures but not in the pituitary leading to normal activity of the hypothalamic–pituitary–adrenocortical (HPA) axis under basal conditions and reduced anxiety-related behavior in the light–dark box and the elevated plus maze (EPM) as compared to wild-type (WT) mice (Müller et al., Nat Neurosci 6:1100–1107, 2003).Objective To identify neurobiological correlates underlying this reduced anxiety-like behavior, the expression of c-Fos, an established marker for neuronal activation, which was examined in response to a mild anxiogenic challenge.Materials and methods Mice were placed for 10 min on the open arm (OA) of the EPM, and regional c-Fos expression was investigated by immunohistochemistry.Results OA exposure enhanced c-Fos expression in both conditional CRF-R1 knockout and WT mice in a number of brain areas (39 of 55 quantified), including cortical, limbic, thalamic, hypothalamic, and hindbrain regions. The c-Fos response in conditional CRF-R1 knockout animals was reduced in a restricted subset of activated neurons (4 out of 39 regions) located in the medial amygdala, ventral lateral septum, prelimbic cortex, and dorsomedial hypothalamus.Conclusions These results underline the importance of limbic CRF-R1 in modulating anxiety-related behavior and suggest that reduced neuronal activation in the identified limbic and hypothalamic key structures of the anxiety circuitry may mediate or contribute to the anxiolytic-like phenotype observed in mice with region-specific deletion of forebrain CRF-R1. 相似文献
13.
Ismail O. Ishola Manavi ChatterjeeSantoshkumar Tota Narender TadigopullaOlufunmilayo O. Adeyemi Gautam PalitRakesh Shukla 《Pharmacology, biochemistry, and behavior》2012,103(2):322-331
The root decoction of Cnestis ferruginea (CF) Vahl DC (Connaraceae) is used in traditional African medicine in the management of psychiatric disorders. This study presents the antidepressant and anxiolytic effects of amentoflavone (CF-2) isolated from the root extract of C. ferruginea.The antidepressant effect was studied using the forced swimming (FST) and tail suspension tests (TST) while the hole-board, elevated plus maze (EPM) and light/dark tests were used to evaluate the anxiolytic effect. Acute treatment with CF extract and amentoflavone significantly (p < 0.001) reduced the duration of immobility in FST and TST with peak effects observed at 100 and 50 mg/kg respectively in comparison to control treated. Antidepressant effects of CF and amentoflavone were significantly higher (p < 0.05) when compared to imipramine in FST but comparable to the fluoxetine treated group in TST.The pretreatment of mice with metergoline (4 mg/kg, i.p., a 5-HT2 receptor antagonist), prazosin (62.5 μg/kg, i.p., an α1-adrenoceptor antagonist), and yohimbine (1 mg/kg, i.p., an α2-adrenoceptor antagonist), but not sulpiride (50 mg/kg, i.p., a dopamine D2 receptor antagonist), cyproheptadine (3 mg/kg, i.p., a 5-HT2 receptor antagonist), atropine (1 mg/kg, i.p., a muscarinic receptor antagonist) 15 mins before the administration of amentoflavone (50 mg/kg; p.o.) significantly prevented its antiimmobility effect in the FST.CF extract and CF-2 significantly (p < 0.05) attenuated anxiety by increasing the number of head-dips in the hole-board test, the time spent on the open arms in the EPM, and the exploration of the light chamber in the light/dark test. Pretreatment with flumazenil (3 mg/kg, i.p., ionotropic GABA receptor antagonist) 15 min before oral administration of amentoflavone (25 mg/kg) significantly reduced the time spent in the open arms in EPM. It is concluded from the results obtained that amentoflavone produces its antidepressant effect through interaction with 5-HT2 receptor and α1-, and α2-adrenoceptors while the anxiolytic effect involved the ionotropic GABA receptor. 相似文献
14.
Increased anxiety-related behavior in mice deficient for metabotropic glutamate 8 (mGlu8) receptor 总被引:2,自引:0,他引:2
Linden AM Johnson BG Peters SC Shannon HE Tian M Wang Y Yu JL Köster A Baez M Schoepp DD 《Neuropharmacology》2002,43(2):251-259
Pre-synaptic metabotropic glutamate (mGlu) receptors modulate neuronal excitability by controlling glutamate and gamma-aminobutyric acid (GABA) release. The mGlu8 receptor is predominantly found in pre-synaptic terminals and its expression is highly restricted. To study the role of this receptor, mGlu8 receptor-deficient mice were generated. Here we report that na?ve mGlu8 receptor-deficient mice showed increased anxiety-related behavior in the elevated plus maze in low illumination conditions (red light). Open arm avoidance and risk assessment behavior were both significantly increased in mutant mice. Increased stressfulness of the testing conditions abolished this behavioral difference. Fluorescent light or prior restraint stress decreased the open arm activity of wild-type mice, while the open arm activity of mutant mice was essentially unaffected, leading to similar values in both strains. The total number of arm entries or closed arm entries was not significantly different between strains, indicating that the lack of mGlu8 receptor does not affect locomotor activity. No gross behavioral changes, or changes in the function of the autonomic nervous system or somatomotor systems were observed in mutant mice. Moreover, no significant differences in seizure susceptibility were detected between strains. Our results suggest that mGlu8 receptor may play a role in responses to novel stressful environment. 相似文献
15.
Byrnes EM 《Psychopharmacology》2005,182(4):537-544
Rationale and objective Opiate abuse in adolescent girls has increased in the past decade; however, few animal studies have examined the potential
consequences of opiate use occurring at this time. The purpose of the present study was to determine whether exposing female
rats to morphine during the peripubertal period can alter the adult behavior of their offspring.
Methods Beginning at 30 days of age, female rats were injected subcutaneously (s.c.) twice daily with either morphine sulfate or saline.
The initial morphine dose of 2.5 mg/kg was increased by 2.5 mg/kg daily for a total of 20 days. Ten days after the final drug
treatment, all subjects were mated. Their subsequent offspring were then tested as adults on the elevated plus maze, in a
novel environment or were examined in a morphine locomotor sensitization paradigm.
Results Adult female offspring of dams exposed to morphine during puberty spent less time in the open arms of the elevated plus maze
and displayed decreased exploration in a novel environment. Female offspring also demonstrated a more rapid induction of morphine
sensitization. Finally, male offspring demonstrated a significant enhancement in the expression of morphine sensitization.
Conclusions Chronic morphine exposure during adolescence can have significant transgenerational effects on adult offspring. Future studies
will be needed to determine how these changes are transferred to the offspring and whether these effects are specific to drug
exposure that occurs during the peripubertal period.
This work was supported by the National Institute on Health grant DA14613 awarded to E.M. Byrnes 相似文献
16.
Frussa-Filho R Barbosa-Júnior H Silva RH Da Cunha C Mello CF 《Psychopharmacology》1999,147(2):168-173
Rationale: Both novelty and naloxone have been reported to modify the anxiolytic-like effect of benzodiazepines in the elevated plus
maze. In addition, it has been largely demonstrated that novelty alters endogenous opioid activity. Objectives: The present study was designed to examine a possible interaction between novelty and naltrexone effects on the behavior of
chlordiazepoxide-treated rats in two animal models of anxiety. Methods: Thirty minutes after acute intraperitoneal treatment with saline or naltrexone and saline or chlordiazepoxide, male Wistar
rats were exposed for the first time to the elevated plus maze apparatus or the social interaction arena for the quantification
of the percentage of time spent in the open arms or the time of active social interaction, respectively. The effects of naltrexone
and/or chlordiazepoxide on the plus maze and the social interaction tests were also evaluated after previous exposure to the
respective apparatus. Results: Naltrexone dose dependently increased the percentage of time spent in the open arms of the elevated plus maze in chlordiazepoxide-treated
(5 mg/kg i.p.) rats exposed for the first time to the apparatus. Similarly, naltrexone (5 mg/kg i.p.) increased the time spent
in active social interaction by chlordiazepoxide-treated rats exposed to an unfamiliar arena. In both experiments, naltrexone
had no effect when administered alone. When both the plus maze and the social interaction tests were conducted after previous
exposure to the respective apparatus, naltrexone did not modify the behavior of chlordiazepoxide- or saline-treated rats. Conclusions: These data suggest that the anxiolytic-like effects of chlordiazepoxide can be modified by opioid mechanisms in novel environments.
Received: 12 February 1999 / Final version: 19 June 1999 相似文献
17.
Roy Corbett Stuart Fielding Michael Cornfeldt Robert W. Dunn 《Psychopharmacology》1991,104(3):312-316
Benzodiazepine (BZD) anxiolytics, through their activation of the BZD-GABA receptor complex, display robust anxiolytic-like effects following systemic administration in both conditioned and non-conditioned behavioral procedures. The present results show that the GABAA agonists muscimol (0.5–1.0 mg/kg), THIP (2.5–10.0 mg/kg), and isoguvacine (25.0 mg/kg) as well as the GABA transaminase (GABA-T) inhibitor AOAA (aminooxyacetic acid; 5.0–20.0 mg/kg) following intraperitoneal administration exert anxiolytic-like activity of similar magnitude to that of diazepam in two nonconditioned procedures, namely the social interaction and the elevated plus maze tests. We have also extended our original findings that the anti-epileptic drug sodium valproate exerts an anxiolytic-like effect in the Geller conflict paradigm, to show this agent's robust activity in the social interaction and elevated plus maze tests following systemic administration (100–400 mg/kg). These results show that GABAergic agents that facilitate GABA transmission are effective following systemic administration in non-conditioned anxiety procedures and may indicate potential therapeutic efficacy in certain anxiety states. 相似文献
18.
Braun AR Heinz AJ Veilleux JC Conrad M Weber S Wardle M Greenstein J Evatt D Drobes D Kassel JD 《Addictive behaviors》2012,37(4):485-491
Individuals who smoke cigarettes are significantly more likely to smoke more when they drink alcohol. Indeed, smoking and drinking appear strongly linked, at both between- and within-person levels of analyses. Anecdotal evidence further suggests that alcohol consumption in combination with smoking cigarettes reduces anxiety, yet the mechanisms by which this may occur are not well understood. The current study assessed the separate and combined effects of alcohol and nicotine on self-reported and psychophysiological (startle eyeblink magnitude) indices of anxiety. Results indicated that alcohol provided anxiolytic benefits alone and in combination with nicotine, as evidenced by significant reductions in startle eyeblink magnitude. According to self-reported anxiety, alcohol and nicotine exerted a conjoint effect on diminishing increases in anxiety subsequent to a speech stressor. These data highlight the importance of studying both the separate and combined effects of these two widely used substances, as well as the advantages of employing a multimodal assessment of emotional response. 相似文献
19.
RATIONALE: Glutamate antagonists microinjected into the dorsolateral PAG (DLPAG) show an anxiolytic-like profile in the elevated plus maze. Other columns of the PAG are also involved in defensive reactions. Few studies, however, have investigated the effects of pharmacological manipulation of the ventrolateral PAG (VLPAG) on procedures that predict anxiolytic activity. OBJECTIVES: To investigate the effects of the NMDA receptor (NMDAr) antagonist 2-amino-7-phosphonoheptanoic acid (AP7) microinjected into the DL or VLPAG in two procedures that predict anxiolytic activity using distinct aversive contingencies, the elevated plus maze and the Vogel punished licking test. METHODS: Male Wistar rats (7-14/group) with cannulas aimed at the DLPAG or VLPAG received AP7 (2 nmol/0.5 microl) or saline and 10 min later were submitted to the behavioural tests. In the punished licking experiment, water deprived (48 h) animals were allowed to drink for 3 min, receiving a 0.5 mA shock every 20 licks. The elevated plus maze test was performed as described elsewhere. Using this test, a dose response-curve for AP7 (0.2-20 nmol) injected in a smaller volume (0.25 microl) into the VLPAG was also performed. RESULTS: AP7 increased exploration of open arms of the EPM when microinjected into either the DLPAG or VLPAG ( P<0.05, ANOVA). The drug also increased the number of punished licks when administered into those columns (ANOVA, P<0.05). CONCLUSIONS: The results suggest that antagonism of endogenous excitatory amino acid neurotransmission in the DLPAG or VLPAG is able to reverse behavioral suppression induced by distinct aversive contingencies. 相似文献
20.
J. C. Thornton S. Dawe C. Lee C. Capstick P. J. Corr P. Cotter S. Frangou N. S. Gray M. A. H. Russell J. A. Gray 《Psychopharmacology》1996,127(1-2):164-173
Latent inhibition (LI) is a phenomenon in which repeated non-reinforced exposure to a stimulus retards subsequent conditioning
to that stimulus; it reflects a process whereby irrelevant stimuli become ignored, and has been the subject of study concerning
attentional abnormalities in schizophrenia. Low doses of the indirect dopamine (DA) agonists, amphetamine and nicotine, disrupt
LI in the rat. These drugs are believed to disrupt LI via DA release in the nucleus accumbens; LI in amphetamine- and nicotine-treated
rats is reinstated by administration of the DA antagonist haloperidol. In human subjects, low doses of amphetamine abolish
LI, and more recently haloperidol has been shown to potentiate LI. The present study investigated the effects of nicotine
on LI in human subjects, and also attempted to replicate the abolition of LI by amphetamine. Nicotine failed to affect LI
when administered either subcutaneously or by cigarette smoking. LI was, however, abolished in a group of subjects given 5
mg amphetamine 90 min before testing. Supplementary analyses of the data pooled from all three experiments showed that, in
contrast to an earlier report, LI was no weaker in smokers than in non-smokers. 相似文献