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Discusses a research on the differential cognitive effects of Ginkgo biloba after acute and chronic treatment in healthy young volunteers. Definition of Ginkgo biloba; Use of the Paced Auditory Serial Addition Task; Information on the pattern recognition memory task.

Rationale: Unconditioned anxiogenic effects of nicotine have been observed in the social interaction (SI) test 5 min after injection of a low dose and both 5 min and 30 min after injection of a high dose. Conditioned anxiety has also been observed 24 h after testing in the SI with a high dose of nicotine. Objectives: In order to determine whether these three anxiogenic effects shared a common mechanism, we investigated the role of corticotropin releasing factor (CRF). We therefore examined whether the CRF antagonist α-helical CRF[sub 9-41] could block these three anxiogenic effects of nicotine. Methods: To test the unconditioned anxiogenic effects, pairs of male rats were tested in SI 5 min after s.c. vehicle or nicotine (0.1 mg/kg) or 30 min after s.c. vehicle or nicotine (0.45 mg/kg), and 30 min after i.c.v, artificial cerebrospinal fluid (aCSF) or a-helical CRF[sub 9-41]. To test conditioned anxiety, rats were exposed to the SI test on day 1, 5 min after vehicle or nicotine (0.1 mg/kg). On day 2, they were re-tested in SI 30 min after i.c.v, aCSF or α-helical CRF[sub 9-41] (5 µg). Results: α-Helical CRF[sub 9-41] did not block the unconditioned anxiogenic effect of either dose of nicotine. Nicotine (0.1 mg/kg, 5 min) elicited a conditioned anxiogenic response that was significantly reversed by α-helical CRF[sub 9-41]. The CRF antagonist alone had no effect. Conclusions: CRF is an important mediator of the conditioned anxiety to nicotine, but may not play a role in mediating the acute anxiogenic effects. [ABSTRACT FROM AUTHOR]

Abstract The 5-HT1A receptor has previously been shown to be important in mediating the behavioural effects of nicotine. It is possible that nicotine administration might regulate the levels of 5-HT receptors in limbic and cortical regions, and such regulations may underlie adaptive responses to nicotine in the central nervous system. The effects of acute and chronic systemic (–)-nicotine administration on 5-HT1A receptor gene expression were measured by in situ hybridization, in the rat cerebral cortex, dorsal hippocampus and lateral septum. In the cortex, acute nicotine (0.5 mg/kg i.p.) significantly increased the expression of 5-HT1A receptor mRNA 2 h and 24 h after injection. Similarly, acute nicotine significantly increased 5-HT1A receptor mRNA in the dentate gyrus (DG), CA3 and CA1 regions of the dorsal hippocampus 2 h and 24 h after injection. Acute nicotine was without effect in the lateral septum. Chronic nicotine (0.5 mg/kg i.p; twice daily for 7 days) significantly decreased 5-HT1A receptor mRNA in the cortex 2 h after the final injection, but was without effect at 24 h or 72 h. Chronic nicotine caused no changes in 5-HT1A mRNA in the lateral septum or dorsal hippocampus. These data demonstrate that nicotine regulates 5-HT1A receptor gene expression in the cortex and hippocampus. The rapid regulation of expression of 5-HT1A receptor mRNA leads to the hypothesis that nicotine-induced 5-HT release may alter the postsynaptic sensitivity to 5-HT. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to determine the role of the 5-HT[sub 1A] receptors in the lateral septum in the mediation of the anxiogenic effects of nicotine in the social interaction and elevated plus maze tests of anxiety in the rat. Bilateral infusion of (-)-nicotine (4 and 8 µg) and of the 5-HT[sub 1A] receptor agonist 8-OH-DPAT (200 and 500 ng) into the lateral septum decreased the time spent in social interaction, indicating anxiogenic effects. The anxiogenic effect of 8-OH-DPAT (500 ng) was completely reversed by coadministration of a behaviourally inactive dose of the 5-HT[sub 1A] receptor antagonist, WAY 100635 (200 ng). The anxiogenic effect of the lower dose of (-)-nicotine (4 µg) was completely reversed by WAY 100635 (200 ng), but the reversal was only partial following administration of 8 µg nicotine. In a second test of anxiety, the elevated plus maze, lateral septal administration of 8-OH-DPAT (500 ng) and nicotine (4 µg) induced anxiogenic effects. In this test, the anxiogenic effect of nicotine (4 µg) was completely reversed by coadministration of WAY 100635 (200 ng). The effects of 8-OH-DPAT demonstrate that stimulation of 5-HT[sub 1A] receptors in the lateral septum has anxiogenic effects in two animal tests and that the anxiogenic effects of nicotine are mediated at least in part by these 5-HT[sub 1A] receptors. [ABSTRACT FROM AUTHOR]

Abstract Rationale: Evidence is starting to accumulate that NK[sub 1] receptor antagonists might have anxiolytic effects in animal tests and in patients. Objective: To examine the effects of NKP608, a substance P antagonist acting at NK[sub 1] receptors, in various conditions of the social interaction test of anxiety and to determine its effects after 3 and 6 weeks of treatment. Methods: Rats were tested after vehicle, 0.01 or 0.1 mg/kg PO in three conditions of the social interaction test that varied in the level of anxiety generated. Thus pairs of rats were tested in an arena with which they were unfamiliar that was lit by high (HU) or low (LU) light and in the condition that generated the lowest level of anxiety, i.e. an arena with which they were familiar, lit by low light (LF). They were also tested after 3 and 6 weeks of treatment with 0.03 mg/kg and after 24 h withdrawal from these chronic treatments. Results: NKP608 had significant anxiolytic effects at 0.01, 0.03 and 0.1 mg/kg PO in the HU and LU test conditions, but was without effect in the LF condition, except for an increased incidence of bite attacks at 0.1 mg/kg. The anxiolytic effect of 0.03 mg/kg remained alter 3 weeks of chronic treatment and there was no anxiogenic effect after 24 h of drug withdrawal. Following 6 weeks of chronic treatment (0.03 mg/kg per day), tolerance had developed, but no anxiogenic withdrawal effect was seen 24 h after the last dose. Conclusions: These results provide further evidence that substance P may play a role in mediating states of anxiety and suggest that the selective NK[sub 1] receptor antagonist NKP608 may prove a useful anxiolytic compound. [ABSTRACT FROM AUTHOR]

Presents information on a study which examined the role of the dorsal hippocampus in bimodal modulation by nicotine of anxiety in the social interaction test. Test conditions; Role of nicotine in which the activity of other neurotransmitters is crucial to its expression; Mediation of anxiogenic effects of the dorsal hippocampus.

Investigates the effects hippocampal cholinergic modulation has on anxiety. Information on the pharmacological mechanisms controlling anxiety; Role of the cholinergic system in anxiety; Methodology and results of the study.

The effect of the treatment dose of diazepam was assessed on the rate of development of tolerance to diazepam's effects on rat behaviour in the elevated plus-maze test of anxiety. Tolerance developed more rapidly when treatment was with the higher dose: after 14 days when rats were given 2.5 mg/kg/day, but not until 21 days when they were given 1 mg/kg/day. When rats were tested undrugged 36 h after the last of 14 daily doses of diazepam (2·5mg/kg) they showed behavioural changes indicating increased anxiety. Rats tested at this time with a lower dose of diazepam (1mg/kg) also showed changes indicating increased anxiety compared with the control scores. This indicates that a more gradual tapering of doses would be necessary to avoid withdrawal responses. [ABSTRACT FROM AUTHOR]

Sodium lactate (60 and 120 mg/kg), isoproterenol (0·1 -0·6 mg/kg), and yohimbine (1·25-5 mg/kg) were investigated in two animal tests of anxiety (the elevated plus-maze and the social interaction test). Rats were also scored for panic-Like behaviour following administration of these panic-inducing agents and following inhalation of air supplemented with CO2 (5 and 20 per cent). None of the drugs changed the time spent in social interaction or evoked panic-like behaviour. In the elevated plus-maze, sodium lactate was without effect. The highest dose of isoproterenol (0·6 mg/kg) reduced the percentage of time spent on the open arms, and yohimbine reduced both the percentage of entries made onto the open arms and the percentage of time spent on the open arms, indicating anxiogenic activity. The lack of a strong anxiogenic profile with the pro-panic compounds suggests that anxiety and panic may be biologically distinct. [ABSTRACT FROM AUTHOR]

The anxiolytic, buspirone, was given to rats in combination with four antidepressants: clomipramine (3-30mg/g), desipramine (5-10mg/kg), maprotiline (5-15mg/kg) and mianserin (10-15mg/kg). Even 2 mg/kg buspirone caused a significant incidence of myoclonic seizures, when combined with clomipramine (30mg/kg). desipramine (5-10mg/kg) and mianserin (15mg/kg). Higher doses of buspirone caused seizures when combined with all doses of the four antidepressants tested. The only antidepressant to cause myoclonus on its own was maprotiline (10 and 15mg/kg). The universality of the incidence of myoclonus precluded any conclusions about the underlying mechanism. However, whilst it is difficult to draw cross-species conclusions, our results would caution against the clinical use of buspirone in combination with antidepressants. [ABSTRACT FROM AUTHOR]

The clinical efficacy of the benzodiazepines in reducing anxiety is widely accepted. However, the search for novel anxiolytics continues, motivated by the hope of finding a non-sedative anxiolytic. This article reviews the pre-clinical evidence for new compounds as it relates both to their anxiolytic actions in animal tests and to their sedative potential. Drugs acting at sites on the GABA-benzodiazepine receptor complex are discussed, as well as the potential importance of aminergic and peptidergic pathways. [ABSTRACT FROM AUTHOR]