Plus-maze Model Of Anxiety Research Articles

The Anxiogenic Effects of Caffeine Do Not Potentiate Nicotine Withdrawal in an Elevated Plus Maze Model of Anxiety

Background: Negative effect during withdrawal is associated with tobacco relapse, yet little is known about factors that increase the aversive symptoms of withdrawal. This study explored how caffei...

Acute high dose of chlorpyrifos alters performance of rats in the elevated plus-maze and the elevated T-maze

Chlorpyrifos (CPF) is a broad spectrum organophosphate (OP) pesticide widely used in agriculture, industry and household. Several animal studies indicate emotional disturbances after CPF exposure, although the results are sometimes puzzling. Thus, both anxiolytic and anxiogenic effects of CPF have been reported in different animal models of anxiety [Sánchez-Amate MC, Flores P, Sánchez-Santed F. Effects of chlorpyrifos in the plus-maze model of anxiety. Behav Pharmacol 2001;12:285–92; Sánchez-Amate MC, Dávila E, Cañadas F, Flores P, Sánchez-Santed F. Chlorpyrifos shares stimulus properties with pentilenetetrazol as evaluated by and operant drug discrimination task. Neurotoxicology 2002;23:795–803; López-Crespo G, Carvajal F, Flores P, Sánchez-Santed F, Sánchez-Amate MC. Time-course of biochemical and behavioural effects of a single high dose of chlorpyrifos. Neurotoxicology 2007;28:541–7]. On the other hand, other behavioural effects of CPF are time-dependent [López-Crespo G, Carvajal F, Flores P, Sánchez-Santed F, Sánchez-Amate MC. Time-course of biochemical and behavioural effects of a single high dose of chlorpyrifos. Neurotoxicology 2007;28:541–7], raising the question that the effects of CPF could be task and post-administration time dependent. To test this hypothesis, three groups of rats were treated with a single high dose of CPF (250 mg/kg); one of the groups was tested on day 5 on the elevated plus-maze, to complete our previous study on day 2 [Sánchez-Amate MC, Flores P, Sánchez-Santed F. Effects of chlorpyrifos in the plus-maze model of anxiety. Behav Pharmacol 2001;12:285–92]. The remaining groups were tested on the elevated T-maze on days 2 and 5. CPF produced an increased open arm activity on the elevated plus-maze on day 5, an increased escape latency on the elevated T-maze on day 2 and an impaired inhibitory avoidance on day 5. Data are discussed taking together all studies carried out in our laboratory, confirming that CPF effects on emotional behaviour are dependent on both task contingencies and post-administration time.

Effects of chlorpyrifos in the plus-maze model of anxiety.

The purpose of the present study was to determine the effect of two different doses of the organophosphate insecticide O,O'-diethyl-O-3,5,6-trichloro-2-pyridylphosphorothionate [chlorpyrifos (CPF)], a cholinesterase (ChE) inhibitor, in the plus-maze test of anxiety in the rat, as well as on acetylcholinesterase (AChE) activity in the brain. In a first experiment, the behavioural methodology was validated by showing the anxiolytic and anxiogenic effects of diazepam and pentylenetetrazole (PTZ), respectively. Acute exposure to CPF (166 mg/kg and 250 mg/kg, s.c.) produced significant dose-dependent inhibition (54% and 71%, respectively) of whole-brain AChE 48 hours after treatment. Neither dose produced signs of acute cholinergic toxicity at any time following treatment, as was verified by a functional observational battery. Both doses of CPF were injected 48 h before testing in the plus-maze and were shown to have anxiogenic effects as demonstrated by the significant decrease in the percentage of time spent and percentage of entries into open arms. This report thus shows clear behavioural alteration as an acute effect of an organophosphate in the absence of any classic sign of cholinergic toxicity. Our results are relevant to the understanding of both the pharmacology of anxiety and the behavioural toxicology of cholinesterase inhibitors.

Epi-inositol: A potential antidepressant

Inositol is a simple polyol precursor in a second messenger system important in the brain. A double-blind controlled trial of 12 g daily of inositol in 28 patients with depression for 4 weeks found significant benefit for inositol compared to placebo on the Hamilton Depression Scale. Because many antidepressants are effective in panic disorder, 21 patients with this disorder completed a double-blind, placebo-controlled crossover treatment trial of inositol 12 g per day. Frequency and severity of panic attacks and severity of agoraphobia declined significantly with inositol treatment compared to placebo. Because serotonin reuptake inhibitors benefit obsessive-compulsive disorder (OCD) and inositol is reported to reverse desensitization of serotonin receptors, 13 patients with OCD completed a double-blind, controlled crossover trial of 18 g inositol or placebo for 6 weeks each. Inositol significantly reduced scores of OCD symptoms compared with placebo. Epi-inositol, an artificial stereoisomer of myoinositol, was found to have effects similar to those of myoinositol in reversing lithium–pilocarpine seizures and in reversing lithium-induced rises in cytidine monophosphorylphosphatidate in cultured cells as does myoinositol. We measured the behavior of rats in an elevated plus-maze model of anxiety after chronic treatment of 11 daily ip injections of epi-inositol, myoinositol, or control solution. Epi-inositol reduced anxiety levels of rats compared with controls, and its effect was stronger than that of myoinositol. Epi-inositol could be a more effective psychoactive drug than its natural analog. Drug Dev. Res. 50:309–315, 2000. © 2000 Wiley-Liss, Inc.

Chronic epi-inositol has an anxiolytic-like effect in the plus-maze model in rats.

Behavioural effects of myo-inositol have been demonstrated in animal models of psychiatric disorders and in clinical trials in psychiatric patients. These effects of myo-inositol were thought to be consequences of its being a substrate for the enzyme phosphatidylinositol (PI) synthase. Recently, epi-inositol, an unnatural stereoisomer of myo-inositol that is not a substrate for PI synthase, was found to also have effects similar to those of myoinositol to reverse lithium-pilocarpine seizures. The present study measured the behaviour of rats in an elevated plus-maze model of anxiety after chronic treatment of 11 daily i.p. injections of epi-inositol, myo-inositol, or control solution. Epi-inositol reduced levels of anxiety-like behaviour in rats compared with controls, and its effect was stronger than that of myo-inositol. The increased relative effect of epi-inositol could be due to slower metabolism or to a different mechanism of action.

Opioid antagonist naloxone potentiates anxiogenic-like action of cholecystokinin agonists in elevated plus-maze.

This study investigated the interplay of cholecystokinin (CCK) and endogenous opioid peptides in the regulation of anxiety. The acute administration of non-selective CCK agonist caerulein (1 and 5 microg/kg) and a selective CCK(B) receptor agonist BOC-CCK-4 (1, 10 and 50 microg/kg) induced a dose-dependent anxiogenic-like action in the plus-maze model of anxiety. BOC-CCK-4 displayed a similar efficacy with caerulein, indicating that the described effect was mediated via CCK(B) receptor subtype. The opioid antagonist naloxone itself (0.5 mg/kg) did not change the exploratory activity of rats in the plus-maze. However, the combination of naloxone with the sub-effective doses of caerulein (1 microg/kg) and BOC-CCK-4 (1 microg/kg) induced a significant inhibition of exploratory behaviour in rats. Accordingly, CCK and endogenous opioid peptides have an antagonistic role in the exploratory model of anxiety in rats.

Neuropharmacological aspects of adaptive pain inhibition in murine “victims” of aggression

This review outlines recent research on a subset of physiological responses in murine “victims” or aggression. In a typical resident-intruder paradigm, the detailed study of intruders has revealed that exposure to conspecific attack (and related stimuli) is associated with two forms of analgesia which appear to be integral components of the murine defensive repertoire. In response to intense/enduring attack, intruder mice display a profound, long-lasting and opioid-mediated analgesia. This reaction is highly correlated with defensive immobility and may function to reduce involuntary cues to further attack. In contrast, the inhibition of pain reactivity in mice tested immediately upon the display of defeat is less intense, shorter-lasting, non-opioid in nature and may function to facilitate active defenses such as escape. As this form of pain inhibition is also evident in intruders exposed to the scent of an aggressive male conspecific, a possible anticipatory defensive function linked to mechanisms of anxiety has been proposed. This hypothesis is supported by 1) the prevention of defeat analgesia by a range of antianxiety drugs (benzodiazepines, 5-hydroxytryptamine1A [5-HT1A] receptor agonists, and 5-HT3 receptor antagonists) and 2) the effects of social defeat on behavior in the elevated plusmaze model of anxiety. These findings are discussed in relation to coping mechanisms in murine “victims” of aggression. © 1995 Wiley-Liss, Inc.

On the effects of lindane on the plus-maze model of anxiety

The behavioral effects of an acute subconvulsant dose of the insecticide and ectoparasiticide γ-hexachlorocyclohexane, lindane, were compared in the plus-maze (+-maze) animal model of anxiety to those elicited by the anxiogenic GABA A-antagonist pentylenetetrazole (PTZ) and the anxiolytic benzodiazepine diazepam. The effects of the coadministration of diazepam and lindane, and of diazepam and PTZ were also studied. The results from the analysis of the data with the multivariate statistical technique principal component analysis indicated that the effects of subconvulsant doses of lindane and PTZ on the behavior of rats in the +-maze are similar, and opposite to those elicited by diazepam, and that the administration of the convulsants would antagonize the effects of the benzodiazepine. The putative anxiogenic properties of the insecticide and the utility of the +-maze model in neurotoxicological research are discussed.

Diazepam—stress interactions in the rat: Effects on autoanalgesia and a plus-maze model of anxiety

On six occasions spaced at least a week apart, two groups of rats were subjected to a variety of stressful conditions consisting of a restraint/bright light complex, either alone or in combination with a tail pinch, whole-body inversion, or partial immersion in cold water. One of these groups was injected with diazepam (2.0 mg/kg) 30 min prior to the stressors, while the other group experienced the drug in their home cages the following day. A third group also received the diazepam but was not exposed to the stressors. In three test sessions all animals were injected with either diazepam or saline and were then exposed to a novel stressor: a plus-maze used as a screening device for anxiolytic drugs. This was immediately followed by a tail-flick measure of analgesia. The longest tail-flick latencies, indicating stress-induced analgesia ("autoanalgesia"), were observed in the group that had not been exposed to stress prior to testing. The other two groups exhibited substantially shorter latencies but did not differ from one another, thus showing a "stress inoculation" effect that was uninfluenced by diazepam. In the plus-maze, diazepam tends to increase the amount of time rats will spend in the two exposed arms of the maze relative to the two enclosed arms. This effect was significantly attenuated in the group that had previously experienced the variety of stressors after a diazepam injection, suggesting a learned association between drug and stress that resulted in a diminution of the drug's anxiolytic property.