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Agonistic behaviour in mice
- Model for anxiolytic, antidepressants and anti-aggressive drugs. The model uses naturally occurring
behaviours of mice such as quantity of social interactions, fighting, defensive-escape behaviour,
exploration of novel environment etc., to quantify the effects of drugs on the response to aversive
stimuli from a strange partner. It has been found that anxiolytics e.g. benzodiazepines selectively
decrease timid activities and disinhibit sociability and locomotion
in timid singly-housed mice; antiaggressive agents e.g. eltoprazine decrease aggressivity and
disinhibit sociability and locomotion in aggressive singly-housed mice; while anxiogenic agents e.g.
beta-CCE or FG 7142 induce a decrease in social interactions and an increase in timid interactions.
Antidepressant activity can be sensitively detected in animals whose normal behaviour
had been "depressed" by drugs, or by other means, and in the presented model the sociability and
locomotion is depressed in singly-housed male mice by the presence of the strange partner.
- Sulcova A., Krsiak M. (1989) Differences among nine 1,4-benzodiazepines: an ethopharmacological
evaluation in mice. psychopharmacology, 97, 157-159.
- Apparatus : metal self-cleaning cages (8 x 16 x 13 cm),standard plastic cages (38 x 22 x 14 cm),
transparent observation boxes (20 x 30 x 20 cm).
- see : Activity (behavioral) Instruments - Ergometric
- Procedure
Induction of psycho-social stress in male rats
- Model of chronic social stress in male rats, where the stress is induced by repeated social defeat. Stressed rats
can be used in pharmacological tests of mood disorders (e.g. anxiety and depression). Since mood
disorders are often associated with chronic stress states, the use of chronically stressed animals
in behavioural tests increase the latter's relevance for the human condition. This series of
studies combines the induction of psycho-social stress in male rats with subsequent testing in a
behaviours test sensitive to anxiolytic, anti-aggression or antidepressant drugs.
- Fuchs E, Kramer M, Hermes B, Netter P and Hiemke C (1996) Psychosocial stress in tree shrews: clomipramine
counteracts behavioral and endocrine changes. Pharmacology Biochemistry and Behavior 54:219-228.
- Apparatus :The test is performed in social interaction cages that are divided
into two compartments by a perforated transparent screen (dimensions: 60x40x50 cm;. walls:
dark grey plastic with the front wall made of transparent plastic; illumination: dim red light;
bedding: saw dust). computer-based behavioural analysis system.
- see : Activity (behavioral) Instruments - Ergometric
- Procedure
Drug treatment of the resident-intruder in rats
- Test of aggressiveness, where an intruder rat is placed into the home-cage of a resident rat and the
attack latency and frequency, the attack pattern and the frequency of offensive and defensive
postures are manually recorded for the resident and the intruder. The test is sensitive to the
action of various compounds such as anxiolytics (e.g. benzodiazepines), antidepressants (e.g. SSRI's),
anti-aggressives, serotonergic, dopaminergic and noradrenergic compounds. Compounds can be tested
either in the resident or in the intruder. If the resident is treated the test is sensitive
to anxiolytic and antidepressant drugs (SSRI¡¯s and tricyclics), whereas if the intruder is
treated the test is sensitive to anti-aggression drugs.
- Grant EC and Mackintosh JH (1963) A comparison of the social postures of some common laboratory
rodents. Behaviour 21: 246-259.
- Apparatus : The test is performed in the home cage of the resident rat (dimensions
: 60x40x50 cm;. walls: dark grey plastic, but the front wall is made of transparent plastic;
illumination: dim red light; bedding: saw dust). The behaviour is recorded on video and analysed
using the computer-based behavioural analysis system.
- see : Activity (behavioral) Instruments - Ergometric
Drug treatment of the resident-intruder in mice
- Test of aggressiveness, where an intruder mouse is placed into the home-cage of a resident mouse and
the attack latency and frequency, the attack pattern and the frequency of offensive and defensive
postures are manually recorded for the resident and the intruder. The test is sensitive to the
action of various compounds such as anxiolytics (e.g. benzodiazepines), antidepressants (e.g.
SSRI's), anti-aggression drugs, serotonergic, dopaminergic and noradrenergic compounds. Compounds
can be tested either in the resident or in the intruder. If the resident is treated the test is
sensitive to anxiolytic and antidepressant drugs (SSRI¡¯s and tricyclics), whereas if the intruder
is treated the test is sensitive to anti-aggression drugs.
- Grant EC and Mackintosh JH (1963) A comparison of the social postures of some common laboratory
rodents. Behaviour 21: 246-259.
- Apparatus : The test is performed in the home cage of the resident mouse (dimensions:
60x40x50 cm;. walls: dark grey plastic, but the front wall is made of transparent plastic;
illumination: dim red light; bedding: saw dust). The behaviour is recorded on video and analysed
using the omputer-based behavioural analysis system.
- see :Activity (behavioral) Instruments - Ergometric
Social contacts in rats developed during local application of drugs
- The method allows the application of drugs into discrete brain sites, and the parallel assessment of behaviour.
The method can be applied in combination with different tests involving social behaviour (e.g.
social interaction and aggression), but also in elevated plus-maze or open field.
- Haller J, Abraham I, Zelena D, Juhasz G, Makara GB and Kruk MR (1998) Aggressive experience affects the sensitivity of neurones towards
pharmacological treatment in the hypothalamic attack area. Behavioral Pharmacology 9: 469-475.
- Apparatus : The test requires in vivo microdialysis probes, pumps and social interaction
cages (dimensions: 60x40x50 cm;. walls: dark grey plastic with the front wall made of transparent
plastic; illumination: dim red light; bedding: saw dust). The behaviour is recorded on video.
- see : Activity (behavioral) Instruments - Ergometric, Microdialysis, and pumps
Variable social stress in female rats
- Model of chronic social stress in female rats. The stressed rats can be used in pharmacological tests of
mood disorders (e.g. anxiety and depression), where the use of stressed rats can increase the
relevance of the pharmacological investigations. The use of female rats is especially relevant since
depression and anxiety disorders are more common in women that in men, while female rats are rarely
used in pharmacological experiments. Crowding was shown to affect emotionality and various
neuroendocrine and brain functions in rats The present series of studies combines the induction of social stress in female rats
with subsequent testing in a behaviours test sensitive to anxiolytic, anti-aggression or
antidepressant drugs.
- Hormone measurements (RIA) in blood samples taken through venous canullae: ACTH, corticosterone, growth hormone,
vasopresssin, oxytocin, prolactin, adrenaline, and noradrenaline.
- Neurotransmitter measurements (HPLC) from brain tissue samples or samples taken through in vivo
microdialysis of discrete brain areas: noradrenaline, adrenaline, dopamine, serotonin, and amino acids
- Bugajski J, Gadek-Michalska A, Borycz J and Glod R (1999) Social stress inhibits the nitric oxide effect on the corticotropin-releasing
hormone- but not vasopressin-induced pituitary-adrenocortical responsiveness.
Brain Research 817: 220-225.
- Apparatus : The method requires individual cages (30x40x20cm) and group cages (40x40x20cm) (illumination:
dim red light during examination; bedding: saw dust). The behaviour is recorded on video and
analysed using the H77 computer-based behavioural analysis system.
- see : Activity (behavioral) Instruments - Ergometric, Microdialysis, and pumps
Mechanistic Tests
- In vitro
- Electrophysiology
- Whole-cell patch clamp recording from cultured rat dorsal root ganglion cells
- Patch clamp recording of Na+ or K+ channels and currents in axons
- Interaction of drugs with ligand-gated ion channels in isolated neurones
- Interaction of drugs with voltage-gated ion channels in isolated neurones
- Neuroprotection against global ischaemia
- Functional assays
- Drug-induced increases in intracellular free calcium concentrations
- Drug-induced release of pituitary hormones
- Interaction of drugs with ligand-gated ion channels in isolated neurones
- Interaction of drugs with voltage-gated ion channels in isolated neurones
- Alpha and muscarinic agonism and antagonism
- Protein kinase
- Protein kinase PKA
- Protein kinase PKC
- Protein kinase Ca-KII
- Receptor binding
- Adrenergic receptors:
- Alpha-1: 3H-prazosin
- Alpha-2: 3H-clonidine
- Beta receptors: 3H-CGP 12177
- Alpha and beta adrenergic agonist and antagonist subtypes
- Benzodiazepine receptors:
- Dopaminergic receptors:
- D-1: 3H-SCH-23390
- D-2/D-3: 3H-Spiperone
- D-2/D-3: 3H-Raclopride
- GABA-receptors:
- Glutamate receptors :
- NMDA receptor: 3H-CGP39653
- Glycine site: 3H-5,7-DCKA
- NMDA ionophore: 3HMK-801
- 1S,3R-ACDP sensitive metabotropic glutamate receptors
- Opoid receptors:
- Mu: 3H-Dihydromorphine
- Mu: 3H-Naloxone
- Delta: 3H-DADLE
- Kappa: 3H-U69593
- Kappa: 3H-Bremazocine
- Serotonergic receptors:
- 5-HT-1A: 3H-8-OH-DPAT
- 5-HT-2A: 3H-Ketanserine
- Voltage dependent calcium channels:
- Second messenger systems
- Measurements of cAMP
- Effect of agonists and antagonists on cAMP accumulation in slices
- Generation of cyclic AMP stimulated with beta-adrenergic agonists
- Measurements of inositol phosphate
- Inositol phosphate stimulated with alfa1-adrenergic agonists
- Inositol phosphate stimulated with metabotropic receptor agonists
- Alpha1 and beta-adrenergic receptors cross-talk
- Ex vivo
- Autoradiography
- Dopamine system:
- D1 receptors: H-SCH 23390
- D2/D3: H-Quinpirole
- D2/D3: H-Raclopride
- D3: H-7-OH-DPAT
- Glutamate system:
- Metabotropic glutamate receptors: H-glutamate
- HPLC
- Drug effects on dopamine and serotonin metabolism
- Neuroanatomy
- n situ hybridisation (mRNA)
- D-1 receptors
- D-2 receptors
- D-3 receptors
- Proenkephalin
- Neuroanatomy
- Early genes, trophic factors, transcriptional factors and other markers of cellular
neurodegeneration
- Peptides, neurotransmitters and their receptors in the brain and endocrine organs of
rodents
- Receptor binding (Estimation of Bmax and Kd based on saturation binding)
- Adrenergic receptors:
- Alpha-1: 3H-prazosin
- Alpha-2: 3H-clonidine
- Beta receptors: 3H-CGP 12177
- Alpha and beta adrenergic agonist and antagonist subtypes
- Benzodiazepine receptors:
- Dopaminergic receptors:
- D-1: 3H-SCH-23390
- D-2/D-3: 3H-Spiperone
- D-2/D-3: 3H-Raclopride
- GABA-receptors:
- Glutamate receptors :
- NMDA receptor: 3H-CGP39653
- Glycine site: 3H-5,7-DCKA
- NMDA ionophore: 3HMK-801
- 1S,3R-ACDP sensitive metabotropic glutamate receptors
- Opoid receptors:
- Mu: 3H-Dihydromorphine
- Mu: 3H-Naloxone
- Delta: 3H-DADLE
- Kappa: 3H-U69593
- Kappa: 3H-Bremazocine
- Serotonergic receptors:
- 5-HT-1A: 3H-8-OH-DPAT
- 5-HT-2A: 3H-Ketanserine
- Voltage dependent calcium channels:
- In vivo
- Drug discrimination
- Operant drug discrimination
- Morris water maze drug discrimination
- Receptor activity
- Adrenergic alpha-1 receptors:
- methoxamine-induced exploratory hyperactivity in rats
- phenylephrine-induced exploratory hyperactivity in rats
- Dopaminergic receptors
- Quinpirole-induced locomotor hyperactivity in rats
- Muscarinic receptors:
- Oxotremorine-induced syndrome in rats
- 5-HT-1A receptors:
- 8-OH-DPAT induced lower lip retraction
- 5-HT-1B receptors:
- RU 24969-induced hyperactivation
- 5-HT-2A receptors:
- DOI-induced wet dog shakes
- 5-HT-2C receptors:
- m-CPP-induced hypolocomotion
- m-CPP-induced hypophagia
½áºê·¦(ServLab) TEL:02-769-1417, FAX: 02-769-1418
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