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Athina Markou

Publications and source records attributed to Athina Markou.

At least 55 records · Page 3Linked to original sources
PubMed2003

Increased motivation for self-administered cocaine after escalated cocaine intake.

Escalation in cocaine self-administration is hypothesized to involve increased motivation to consume cocaine. The present study determined the effects of escalated cocaine self-administration in rats on the cocaine dose-response function under a progressive ratio schedule. Two groups of rats were allowed to self-administer cocaine under a fixed ratio schedule, for 1 h (ShA; n = 7) or 6 h (LgA; n = 6) per day. The subjects were then allowed to self-administer five doses of cocaine (0, 0.031, 0.063, 0.125 and 0.25 mg/infusion) under a progressive ratio schedule. The dose-response function was shifted upwards in the LgA compared to the ShA group. In conclusion, the present data suggest that escalation in cocaine self-administration is associated with a significant increase in the incentive motivational value of self-administered cocaine.

Animals↗
PubMed2003

Clozapine treatment attenuated somatic and affective signs of nicotine and amphetamine withdrawal in subsets of rats exhibiting hyposensitivity to the initial effects of clozapine.

BACKGROUND: Based on the phenomenologic similarity between symptoms of drug withdrawal and the negative symptoms of schizophrenia (e.g., anhedonia), we hypothesized that treatment with clozapine may be effective against nicotine and amphetamine withdrawal. METHODS: A rate-independent discrete-trial threshold procedure was used to assess brain stimulation reward in rats prepared with electrodes in the lateral hypothalamus. Somatic signs of nicotine withdrawal were also assessed. RESULTS: Clozapine administration (.75 or 1.5 mg/kg) during nicotine or amphetamine withdrawal did not affect the threshold elevations associated with drug withdrawal. The.75 mg/kg clozapine dose reversed the increased number of somatic signs of nicotine withdrawal. Ten days of clozapine treatment (3 mg/kg/b.i.d.) before exposure to nicotine prevented the threshold elevations in a subset of rats and the increases in somatic signs in all subjects. Fourteen-day pretreatment with clozapine (6 mg/kg/day) decreased the duration of amphetamine withdrawal. CONCLUSIONS: Correlational analyses indicated that the ability of clozapine to prevent the affective aspects of drug withdrawal depended on low sensitivity to acute clozapine under baseline conditions. The results are consistent with the clinical situation where clozapine is partially effective against the negative symptoms of schizophrenia and more effective in some individuals than others. These results indicate that lack of sensitivity to the initial negative effects of clozapine may predict its a subsequent therapeutic response. Finally, the data suggest that there may be commonalities in the neurosubstrates mediating affective aspects of drug withdrawal and the negative symptoms of schizophrenia.

Affective Symptoms↗
PubMed2003

Non-nicotinic neuropharmacological strategies for nicotine dependence: beyond bupropion.

Smoking is a major health problem and is propelled, at least in part, by the addictive properties of nicotine. Two types of pharmacological therapies have been approved for smoking cessation by the US Food and Drug Administration. The first therapy consists of nicotine replacement, substituting the nicotine from cigarettes with safer nicotine formulations. The second therapy is bupropion (Zyban), an atypical antidepressant, whose use has raised much debate as to how a non-nicotine-based agent can aid in smoking cessation. This review focuses on recent advances that could lead to the development of improved novel pharmacological treatments. These strategies focus on altering reward processes in the brain by modulating various neurotransmitter systems: the most promising include dopamine D(3) receptor antagonists, noradrenaline reuptake inhibitors, GABA(B) receptor agonists, metabotropic glutamate 5 (mGluR5) receptor antagonists, cannabinoid CB1 receptor antagonists, and corticotropin releasing factor (CRF) 1 receptor antagonists.

Animals↗
PubMed2003

The GABAB receptor agonists baclofen and CGP44532 decreased nicotine self-administration in the rat.

RATIONALE: Previous work has indicated a potential role for gamma-aminobutyric acid-B (GABA(B)) receptor agonists in treating drug addiction in humans. Specifically, GABA(B) receptor agonists decreased cocaine, heroin and nicotine self-administration in rats. OBJECTIVES: The purpose of the present studies was to extend previous findings by assessing the effects of additional GABA(B) receptor agonists on nicotine self-administration and food-maintained responding, under both fixed and progressive ratio schedules in rats. METHODS: Male Wistar rats were exposed to a progressive ratio schedule where various nicotine doses were made available according to a within-subjects Latin Square design. Additional groups of rats were used to test the effects of the GABA(B) receptor agonists baclofen and CGP44532 on nicotine self-administration (0.01 and 0.03 mg/kg per infusion) and food-reinforced responding on fixed and progressive ratio (CGP44532 only) schedules. RESULTS: Nicotine maintained stable self-administration under a progressive ratio schedule with a linear dose-response function ( r=0.61). Both CGP44532 and (-)baclofen dose-dependently reduced nicotine self-administration on the fixed ratio schedule, and also decreased food-maintained responding at higher doses. Further, CGP44532 decreased breakpoints for nicotine and food at identical doses under the progressive ratio schedule. CONCLUSION: The present data demonstrate that administration of GABA(B) receptor agonists decreased intravenous nicotine self-administration under both fixed and progressive ratio schedules of reinforcement, possibly reflecting reduced rewarding effects of nicotine. Both baclofen and CGP44532 exhibited specificity for nicotine- versus food-maintained responding on the fixed ratio schedules but not on the progressive ratio schedule (CGP44532 tested only), indicating the potential usefulness of GABA(B) receptor agonists as therapeutics for smoking cessation.

Animals↗
PubMed2003

Decreased prepulse inhibition during nicotine withdrawal in DBA/2J mice is reversed by nicotine self-administration.

We characterized spontaneous and mecamylamine-precipitated nicotine withdrawal using intravenous nicotine self-administration, the acoustic startle response, prepulse inhibition and somatic signs of withdrawal in DBA/2J mice. Nicotine dependence was induced by continuous nicotine infusion through osmotic minipumps. Nicotine self-administration was studied before and after the induction of dependence. The initial test revealed significant nicotine self-administration at the 0.048 microg/infusion dose. During the second self-administration test, saline-treated mice exhibited increased aversiveness of response-contingent infusions of high nicotine doses; these changes were not seen in the nicotine-treated animals reflecting tolerance to nicotine's effects. Neither mecamylamine administration nor spontaneous withdrawal affected the expression of somatic signs, except that increases in jumping were observed during spontaneous withdrawal. Finally, nicotine withdrawal increased general activity in the startle chambers when no stimuli were presented, possibly reflecting increased body tremor and/or agitation, and decreased prepulse inhibition reflecting a sensorimotor gating deficit; the last two effects were reversed by nicotine self-administration. Thus, nicotine withdrawal results in modest, but yet detectable, changes in the behavior of mice.

Animals↗
PubMed2003

Withdrawal from chronic amphetamine induces depressive-like behavioral effects in rodents.

BACKGROUND: Amphetamine withdrawal and major depression share many behavioral commonalities in humans. Therefore, the examination of the behavioral effects of amphetamine withdrawal in rodents may provide insights into the neurobiological mechanisms underlying both disorders and aid in the development of animal models of depression that are sensitive to antidepressant agents. METHODS: We examined the behavioral effects of withdrawal from chronic continuous infusion of amphetamine (via minipump) in three behavioral paradigms: the intracranial self-stimulation (ICSS) procedure in rats, the modified forced swim test in rats, and the tail suspension test in mice. RESULTS: Amphetamine withdrawal resulted in a prolonged (5 day) deficit in brain reward function as assessed by elevations in ICSS thresholds. Using a similar regimen of amphetamine administration, we examined the behavioral effects of withdrawal in a modified rat forced swim test. Animals that were treated with the highest dose of amphetamine (10 mg/kg/day) exhibited increased climbing behavior and decreased immobility 24 hours after withdrawal; by the 48-hour testing time point, this effect had dissipated. In contrast, animals that had been pretreated with 5 mg/kg/day amphetamine exhibited a pronounced increase in immobility indicative of an increase in "depressive-like" behavior, coupled with decreases in swimming and climbing. In the mouse tail suspension test, both regimens of amphetamine pretreatment induced increases in immobility scores, also indicative of "depressive-like" behavior, 24 hours following withdrawal. CONCLUSIONS: Withdrawal from chronic amphetamine administration results in behavioral changes that may be analogous to some aspects of depression in humans, such as reward deficits (i.e., elevations in brain reward thresholds) and behaviors opposite to those seen after treatment with antidepressant drugs, such as decreased immobility in the forced swim test and the tail suspension test.

Amphetamine↗
PubMed2003

Group II metabotropic and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainate glutamate receptors regulate the deficit in brain reward function associated with nicotine withdrawal in rats.

This study investigated the role of ionotropic and metabotropic glutamate receptors in the deficits in brain reward function, as measured by elevations in intracranial self-stimulation (ICSS) reward thresholds, associated with nicotine withdrawal. The group II metabotropic glutamate (mGluII) receptor agonist LY314582 [a racemic mixture of LY354740 ([+]-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid])] (2.5-7.5 mg/kg) precipitated withdrawal-like elevations in ICSS thresholds, a sensitive measure of reward function, in nicotine-dependent but not control rats. LY314582 did not affect response latencies, a measure of performance in the ICSS paradigm. Bilateral microinfusion of LY314582 (10-100 ng/side) into the ventral tegmental area likewise precipitated dose-dependent threshold elevations in nicotine-dependent rats. Furthermore, a single injection of the mGluII receptor antagonist LY341495 (2S-2-amino-2-[1S,2S-2-carboxycyclopropan-1-yl]-3-[xanth-9-yl]propionic acid) (1 mg/kg) attenuated the threshold elevations observed in rats undergoing spontaneous nicotine withdrawal. mGluII receptors are primarily located on glutamatergic terminals throughout the mesocorticolimbic system, where they act as inhibitory autoreceptors. To investigate whether mGluII receptors contributed to nicotine withdrawal by decreasing glutamatergic transmission, we next examined whether direct blockade of postsynaptic glutamate receptors precipitated withdrawal-like reward deficits in nicotine-dependent rats. The alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainate receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline (NBQX; 0.01-1 mg/kg) precipitated withdrawal-like threshold elevations in nicotine-dependent but not control rats, whereas 6-methyl-2-[phenylethynyl]-pyridine (MPEP; 0.01-3 mg/kg) and dizocilpine (MK-801; 0.01-0.2 mg/kg), antagonists at metabotropic glutamate 5 and N-methyl-d-aspartate receptors, respectively, did not. Overall, these data demonstrate that mGluII receptors play an important role in the reward deficits associated with nicotine withdrawal. Furthermore, it is likely that mGluII receptors generate this reward deficit, at least in part, by decreasing glutamate transmission at AMPA/kainate receptors.

Animals↗
PubMed2003

Effects of repeated withdrawal episodes, nicotine dose, and duration of nicotine exposure on the severity and duration of nicotine withdrawal in rats.

RATIONALE: The aversive aspects of nicotine withdrawal contribute to high relapse rates to tobacco smoking after cessation attempts. OBJECTIVES: To investigate the influence of nicotine dose, duration of nicotine exposure, and withdrawal history on the severity of nicotine withdrawal in rats, as assessed by brain stimulation reward thresholds and somatic signs of withdrawal. METHODS: Repeated spontaneous and precipitated withdrawals were investigated through four successive removals of osmotic minipumps delivering nicotine/saline, or with daily injections of the nicotinic receptor antagonist dihydro-beta-erythroidine during chronic nicotine/saline exposure, respectively. The effects of dose and duration of exposure were investigated using minipumps of varying duration delivering different nicotine doses. RESULTS: Increased duration of nicotine exposure: a). prolonged the duration but did not alter the magnitude of withdrawal-associated threshold elevations; b). increased somatic signs early during withdrawal. Increased total nicotine exposure (i.e. increased dose and exposure duration) increased the duration of threshold elevations (no effect on magnitude) but had no effect on somatic signs. Neither repeated spontaneous nor repeated precipitated withdrawals altered the magnitude of withdrawal significantly. CONCLUSIONS: Increases in total nicotine dose resulted in increased severity of the affective aspects of withdrawal. Further, continuous drug exposure resulted in longer lasting withdrawal than intermittent administration even when the total nicotine dose was the same. There was no correlation between threshold elevations and somatic signs of withdrawal. In conclusion, the severity of nicotine withdrawal is mitigated by characteristics of the drug exposure regimen such as drug dose, duration of exposure and whether exposure is continuous or intermittent.

Animals↗
PubMed2003

Bupropion enhances brain reward function and reverses the affective and somatic aspects of nicotine withdrawal in the rat.

RATIONALE: Bupropion is an atypical antidepressant and the only non-nicotine-based therapy approved for smoking cessation. Its use has raised much debate as to how a non-nicotine-based agent can aid in smoking cessation. OBJECTIVES: We assessed the effects of bupropion on brain reward function under baseline conditions and subsequent to withdrawal from chronic nicotine administration in rats. METHODS: A discrete-trial intracranial self-stimulation paradigm procedure was used that provides one with current intensity thresholds, a measure of reward in rats under baseline conditions and subsequent to withdrawal from chronic nicotine (3.16 mg/kg per day for 7 days via osmotic minipump). Somatic signs were recorded based on a checklist of nicotine abstinence signs in animals withdrawn from nicotine. RESULTS: Bupropion (10-60 mg/kg) dose-dependently lowered reward thresholds in non-withdrawing subjects indicating an increase in reward. Interestingly, a sub-effective dose of bupropion (5 mg/kg) blocked completely the threshold lowering effects of acute nicotine (0.25 mg/kg). Animals withdrawn from chronic nicotine exhibited increases in somatic signs of withdrawal and elevated brain reward thresholds, which is indicative of "diminished interest or pleasure" (i.e. anhedonia) in the rewarding stimuli. Bupropion (10-40 mg/kg) reversed both the reward deficit and the somatic signs, with the highest dose (40 mg/kg) inducing a protracted reversal of the threshold elevation. CONCLUSIONS: Bupropion acts on multiple levels to alter brain reward circuits influenced by nicotine, in addition to reducing the expression of somatic signs of withdrawal. First, bupropion, unlike other antidepressants, increases brain reward function under baseline conditions in non-withdrawing subjects. Second, at low doses bupropion blocks the rewarding effects of nicotine. Third, bupropion reverses the negative affective aspects of nicotine withdrawal. Such actions are likely to act in concert to mediate the unique anti-smoking properties of bupropion.

Animals↗
PubMed2003

The mGluR5 antagonist MPEP decreased nicotine self-administration in rats and mice.

RATIONALE: Nicotine increases glutamate release in the ventral tegmental area and the nucleus accumbens, and thus enhances dopamine neurotransmission in the mesolimbic system that has been implicated in mediating the rewarding effects of drugs. Metabotropic glutamate receptors 5 (mGluR5) are found in the nucleus accumbens and may play a role in modulating the post-synaptic response to both glutamate and dopamine. OBJECTIVES: The present study investigated the effects of the mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) on intravenous nicotine self-administration in Wistar rats and DBA/2J mice. METHODS: Rats were allowed to self-administer nicotine (0.01, 0.03 mg/kg per infusion) or respond for food on one of two fixed-ratio 5 schedules of reinforcement. Drug-naive mice were acutely exposed, in pairs, to nicotine (0, 0.016, 0.048, 0.16, 0.48 microg per infusion) self-administration under a fixed ratio 1 schedule of reinforcement, with one subject controlling the delivery of nicotine to both subjects in each pair. RESULTS: MPEP (1-9 mg/kg) dose-dependently reduced nicotine self-administration with no effect on food-maintained responding in the rats. Self-administration of nicotine was obtained only at the 0.048 microg per infusion dose by the mice, and administration of MPEP (5-20 mg/kg) decreased nicotine self-administration response rates in the mice. CONCLUSIONS: These results indicate that blockade of mGluR5 decreased nicotine self-administration in both rats and mice, and are consistent with findings showing a role of mGluR5 in cocaine self-administration. It is postulated that mGluR5 plays an essential role in mediating the reinforcing effects of nicotine, possibly but not exclusively, via modulation of mesolimbic dopaminergic neurotransmission.

Animals↗
PubMed2003

Withdrawal from chronic phencyclidine treatment induces long-lasting depression in brain reward function.

Phencyclidine (PCP) is a drug of abuse that has rewarding and dysphoric effects in humans. The complex actions of PCP, and PCP withdrawal in particular, on brain reward function remain unclear. The purpose of the present study was to characterize the effects of withdrawal from acute and chronic PCP treatment on brain reward function in rats. A brain stimulation reward procedure was used to evaluate the effects of acute PCP injection (0, 5, or 10 mg/kg) or chronic PCP treatment (0, 10, 15, or 20 mg/kg/day for 14 days delivered via subcutaneous osmotic minipumps) on brain reward function. Withdrawal from acute administration of 5 and 10 mg/kg PCP produced a decrease in brain reward function as indicated by a sustained elevation in brain reward thresholds. When administered chronically, 10, 15, or 20 mg/kg/day PCP induced a progressive dose-dependent potentiation of brain stimulation reward, while cessation of the treatment resulted in significant elevations in reward thresholds reflecting diminished reward. Specifically, withdrawal from 15 or 20 mg/kg/day PCP induced a depression in brain reward function that lasted for the entire month of observation. These results indicate that prolonged continuous administration of high PCP doses facilitates brain stimulation reward, while withdrawal from acute high PCP doses or chronic PCP treatment results in a protracted depression of brain reward function that may be analogous to the dysphoric and anhedonic symptoms observed in PCP dependence, depression, and schizophrenia.

Animals↗
PubMed2003

Characterization of the effects of bupropion on the reinforcing properties of nicotine and food in rats.

Bupropion is an atypical antidepressant drug that is the only nonnicotine-based prescription medicine approved for smoking cessation by the Food and Drug Administration. The aim of the present experiments was to investigate the effects of bupropion (5-40 mg/kg) on the reinforcing properties of nicotine and food in rats. The effects of bupropion were studied under two schedules of reinforcement: a fixed ratio 5 time-out 20-sec (FR5 TO20 s) and a progressive ratio (PR). Rats were trained to respond for nicotine (0.01 or 0.03 mg/kg/infusion, free base) or food under the FR5 TO20 s schedule. Pretreatment with the highest dose of bupropion (40 mg/kg) resulted in a significant reduction (approximately 50%) of nicotine intake in rats self-administering 0.03 mg/kg/infusion of nicotine. The same dose of bupropion also decreased (approximately 40%) the self-administration of 0.01 mg/kg/infusion of nicotine, but this effect did not reach statistical significance. Pretreatment with bupropion slightly (approximately 15%) reduced responding for food under the FR5 TO20 s schedule. Finally, pretreatment with bupropion did not affect the self-administration of nicotine (0.03 mg/kg/infusion) under a PR schedule, but dose-dependently increased responding for food under the same PR schedule. These findings indicate that a high dose of bupropion decreases the reinforcing properties of nicotine as measured under an FR schedule, while having no apparent effects on breaking points for nicotine under a PR schedule that reflects both the reinforcing properties and the motivation to obtain nicotine.

Animals↗
PubMed2003

Conditioned facilitation of brain reward function after repeated cocaine administration.

Cocaine lowers brain reward thresholds, reflecting increased brain reward function. The authors investigated whether, similar to acute cocaine administration, cocaine-predictive conditioned stimuli would lower intracranial self-stimulation (ICSS) thresholds. Rats received a saline injection for 5 days, a cocaine injection (10 mg/kg) for 20 consecutive days, then saline for 5 additional days. Thresholds were measured immediately before and 10 min after each injection. The initial 5 saline injections had no effect on thresholds, whereas cocaine significantly lowered thresholds for 20 days. There was no tolerance or sensitization to this effect of cocaine over days. During the last 5 days when cocaine administration was substituted with saline, rats demonstrated a conditioned lowering of thresholds during the 2nd daily ICSS session. These data demonstrate that cocaine-predictive conditioned stimuli induce a conditioned facilitation of brain reward function.

Animals↗
PubMed2003

Lack of depression-like effects of saccharin deprivation in rats: forced swim test, differential reinforcement of low rates and intracranial self-stimulation procedures.

In humans and laboratory animals, drug withdrawal often is associated with depression-like behaviors. In the present study, rats had unlimited free-choice access to water and a saccharin-containing solution before being subjected to repeated episodes of saccharin deprivation. Saccharin deprivation (1) reduced immobility time in the forced swim test, (2) increased reinforcement rate in rats trained to lever-press under the differential reinforcement of a low-rate (72-sec) schedule of food reinforcement, and (3) lowered intracranial self-stimulation thresholds in a discrete-trial current titration procedure. Taken together, these findings suggest that deprivation from a nondrug reinforcer, saccharin, is not associated with depression-like behaviors. In contrast, saccharin-deprived rats demonstrated improved performance in the behavioral paradigms used here.

Animals↗
PubMed2003

Low dose cocaine self-administration transiently increases but high dose cocaine persistently decreases brain reward function in rats.

This study investigated the effects of self-administered cocaine on brain reward function, measured by intracranial self-stimulation (ICSS) reward thresholds in rats. Self-administration of 10 and 20 cocaine injections (0.25 mg per injection, equivalent to 4.94 +/- 0.23 and 9.88 +/- 0.46 mg/kg, self-administered over 40 +/- 6.9 and 99 +/- 11.9 min, respectively) lowered reward thresholds 15 min later, indicating a facilitation of rewarding ICSS, but had no effect at 2, 24 or 48 h after administration. Thus, self-administration of low cocaine doses did not cause persistent changes in brain reward function. Forty cocaine injections (19.64 +/- 0.94 mg/kg; self-administered over 185 +/- 10.9 min) also transiently lowered reward thresholds 15 min later, while significant threshold current elevations were observed at 2 and 24 h after administration, indicating persistent withdrawal-like reward deficits. Finally, 80 cocaine injections (39.53 +/- 1.84 mg/kg, self-administered over 376 +/- 19.9 min) significantly elevated thresholds 2 and 48 h after self-administration, but not at 24 h. Threshold currents also tended to be elevated 15 min after self-administration. Overall, these data suggest that as the amount of self-administered cocaine increases the motivation to consume further cocaine may be shifted, from obtaining the rewarding actions of cocaine to avoidance and alleviation of a cocaine-induced negative affective state.

Animals↗
PubMed2002

Cocaine-seeking behavior after extended cocaine-free periods in rats: role of conditioned stimuli.

RATIONALE: Cocaine abstinence symptoms and conditioned stimuli (CSs) previously associated with cocaine administration are postulated to contribute to relapse to drug taking in humans. OBJECTIVE: The present study assessed the role of both non-contingent CS presentation and experimenter-imposed extended cocaine-free periods on cocaine-seeking behavior in rats. METHODS: A fixed interval (FI) second-order schedule of intravenous cocaine (0.5 mg/infusion) reinforcement of the type FI 15 min (fixed ratio 8:S) was used. RESULTS: Non-contingent CS presentation before exposure to a cocaine binge had no effect on responding under the second-order schedule of reinforcement for cocaine after 23 h of no access to cocaine. By contrast, six non-contingent presentations of the CS during a 1-min period before the test session increased the number of responses in both no-binge (daily 2-h sessions, five infusions) and binge (two 12-h overnight sessions; maximum 48 infusions) exposed rats on day 7 of the cocaine-free period compared to no-binge- and binge-exposed rats that were not presented with the CSs. On day 30 of the cocaine-free period, only binge-exposed rats presented with the CSs exhibited a tendency for increased level of responding. CONCLUSIONS: The results indicated that non-contingent CS presentation had no effect after 23 h of no access to cocaine, increased drug-seeking behavior on day 7 of the cocaine-free period independent of binge exposure, and a strong tendency to increase drug-seeking behavior only in binge-exposed rats, on day 30 of the cocaine-free period, illustrating the interactive effects of conditioned stimuli with the extended cocaine-free period.

Animals↗
PubMed2002

Effects of antalarmin, a CRF type 1 receptor antagonist, on anxiety-like behavior and motor activation in the rat.

Molecular studies point to a role for the type 1 corticotropin-releasing factor receptor (CRF(1)) in anxiogenic-like and activating effects of CRF and stress. However, CP-154,526, a selective CRF(1) antagonist, has yielded mixed results in such tests. Few studies have examined the behavioral effects of other CRF(1) antagonists. Therefore, we examined the effects of antalarmin, a structurally related analog of CP-154,526, on anxiety-like behavior and motor activation. Antalarmin blocked the anxiogenic-like effect of CRF in the elevated plus maze, without affecting anxiety-like behavior in vehicle-treated animals. Antalarmin decreased spontaneous defensive withdrawal behavior in a novel, brightly illuminated open field. Finally, antalarmin blocked the activating effects of CRF, but not D-amphetamine, without producing motor sedation. These findings indicate that the CRF(1) receptor mediates anxiogenic-like effects of novelty stress and the anxiogenic-like and activating effects of CRF and support the hypothesis that CRF(1) antagonists may be useful for the pharmacotherapy of pathological anxiety.

Animals↗