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Do imidazole behavioral effects in rats reflect its anxiogenic activity?
PharmacologicalReseamhCommunica~n~VoL2~Supp/ementt1988
29
DO IMIDAZOLE BEHAVIORAL EFFECTS IN RATS REFLECT ITS ANXIOGENIC ACTIVITY? F.Ferrari and V.
Mangiafico
Institute of Pharmacolgy, University of Modena, Italy
Imidazole (IMID), which is mainly known as a phosphodiesterase activator and inhibitor of microsomal drug metabolism,exhibits behavioural effects in animal models (Ferrari et al 1986 a, Ferrari et al 1987 a ,b) indicative of a potent influence on CNS dopaminergic (DA) and/or noradrenergic (NA) systems. Moreover, IMID displays many pharmacological similarities with yohimbine (YOH)
(Ferrari et al 1986 b) a selective adrenoceptor
antagonist, at low doses, which induces an anxiety -like state in animals and humans (Lang and Gershon 1963).
These findings
prompted us to evaluate, through behavioural tests, the possible effect of IMID on rat emotionality and arousal.
IMID (75 -
300 mg/Kg i.p.) produced a pronounced state of alertness in rats evidentiated by, abnormal response to acoustic stimuli, accompanied, in the case of the highest doses, by tremor, piloerection and head/body shakes. In the open-field test, IMID (37.5- 300 mg/Kg i.p.) inhibited crossing and rearing in a dose-dependent fashion, this effect being long lasting (about three hours at 75 mg/Kg). YOH (1, 5, and i0 mg/Kg i.p.) and FG 7142 ( 5 mg/Kg i.p. ), two treatments described as anxiogenic in animals and in man, inhibited the activity of rats similarly to IMID. Various drugs, known anxiolitics and others, were administered before IMID; for purposes of
0031-6989/88/20S10029-2/$03.00/0
© 1988 The Italian Pharmacological Society
PharmacobgicalResea~hCommunica~n~Vo~2~ Supp~mentL1988
30
comparison some of them were also administered before YOH and FG 7142. Since the results obtained suggested the possibility that IMID effects in the open-field might reflect an anxietylike state,
this hypothesis was investigated by means of social
interaction and X-maze, two tests considered highly specific for anxiety studies. The data obtained show that IMID depresses social interactions only at doses ihibiting motor activity; YOH, in our experimental conditions,
produced a similar effect.
In a elevated X-maze, with alternating open and closed arms, IMID (37.5 and 75 mg/Kg i.p.) decreased the proportion of open~ arm entries and the time spent in them, without modifying the number of total arm entries; diazepam pretreatment.
this effect was prevented by
In conclusion,
the results obtained and
the possible receptors involved are discussed;
IMID is proposed
as pharmacological tool in the investigation of the neurochemicol mechanisms underlying anxiety.
REFERENCES:
Ferrari F.,Ferrari P.,Baggio G. and Mangiafico V.(1986 a) Arch. Int Pharmacodyn Ther 282:209-221. Ferrari F.,Martinelli R. and Baggio G. (1986 b) Psychopharmacol 88:58-62. Ferrari F.,Tampieri A. and Mangiafico V. (1987 a) Life Sci. 40: 2343-2349. Ferrari F.,Baggio G. and Mangiafico V. (1987 b) Psychopharmacol 93:19-24. Lang W.J. and Gershon S. (1963) Arch. Int Pharmacodyn Ther 142:3-4.
29
DO IMIDAZOLE BEHAVIORAL EFFECTS IN RATS REFLECT ITS ANXIOGENIC ACTIVITY? F.Ferrari and V.
Mangiafico
Institute of Pharmacolgy, University of Modena, Italy
Imidazole (IMID), which is mainly known as a phosphodiesterase activator and inhibitor of microsomal drug metabolism,exhibits behavioural effects in animal models (Ferrari et al 1986 a, Ferrari et al 1987 a ,b) indicative of a potent influence on CNS dopaminergic (DA) and/or noradrenergic (NA) systems. Moreover, IMID displays many pharmacological similarities with yohimbine (YOH)
(Ferrari et al 1986 b) a selective adrenoceptor
antagonist, at low doses, which induces an anxiety -like state in animals and humans (Lang and Gershon 1963).
These findings
prompted us to evaluate, through behavioural tests, the possible effect of IMID on rat emotionality and arousal.
IMID (75 -
300 mg/Kg i.p.) produced a pronounced state of alertness in rats evidentiated by, abnormal response to acoustic stimuli, accompanied, in the case of the highest doses, by tremor, piloerection and head/body shakes. In the open-field test, IMID (37.5- 300 mg/Kg i.p.) inhibited crossing and rearing in a dose-dependent fashion, this effect being long lasting (about three hours at 75 mg/Kg). YOH (1, 5, and i0 mg/Kg i.p.) and FG 7142 ( 5 mg/Kg i.p. ), two treatments described as anxiogenic in animals and in man, inhibited the activity of rats similarly to IMID. Various drugs, known anxiolitics and others, were administered before IMID; for purposes of
0031-6989/88/20S10029-2/$03.00/0
© 1988 The Italian Pharmacological Society
PharmacobgicalResea~hCommunica~n~Vo~2~ Supp~mentL1988
30
comparison some of them were also administered before YOH and FG 7142. Since the results obtained suggested the possibility that IMID effects in the open-field might reflect an anxietylike state,
this hypothesis was investigated by means of social
interaction and X-maze, two tests considered highly specific for anxiety studies. The data obtained show that IMID depresses social interactions only at doses ihibiting motor activity; YOH, in our experimental conditions,
produced a similar effect.
In a elevated X-maze, with alternating open and closed arms, IMID (37.5 and 75 mg/Kg i.p.) decreased the proportion of open~ arm entries and the time spent in them, without modifying the number of total arm entries; diazepam pretreatment.
this effect was prevented by
In conclusion,
the results obtained and
the possible receptors involved are discussed;
IMID is proposed
as pharmacological tool in the investigation of the neurochemicol mechanisms underlying anxiety.
REFERENCES:
Ferrari F.,Ferrari P.,Baggio G. and Mangiafico V.(1986 a) Arch. Int Pharmacodyn Ther 282:209-221. Ferrari F.,Martinelli R. and Baggio G. (1986 b) Psychopharmacol 88:58-62. Ferrari F.,Tampieri A. and Mangiafico V. (1987 a) Life Sci. 40: 2343-2349. Ferrari F.,Baggio G. and Mangiafico V. (1987 b) Psychopharmacol 93:19-24. Lang W.J. and Gershon S. (1963) Arch. Int Pharmacodyn Ther 142:3-4.