Pindolol antagonizes the effects on hippocampal rhythmical slow activity of clonidine, baclofen and 8-OH-DPAT, but not chlordiazepoxide and sodium amylobarbitone.
Buspirone, benzodiazepines, barbiturates and ethanol all reliably reduce the frequency of reticular-elicited hippocampal rhythmical slow activity. In the present experiments we tested a number of drugs which are not usually used for treating generalized anxiety disorders but which have been reported to have some anxiolytic properties. Clonidine (0.3 mg/kg, i.p.), baclofen (6 mg/kg, i.p.) and 8-hydroxy-di-n-propylamino tetralin (8-OH-DPAT) (2.5 mg/kg, i.p.) all reduced the frequency of rhythmical slow activity. The effect of all three drugs was reduced by the 5-hydroxytryptamine 1a antagonist pindolol (2 mg/kg, i.p.). Pindolol had no effect on the reduction in rhythmical slow activity produced by sodium amylobarbitone, as has been previously reported for the benzodiazepine chlordiazepoxide. Flumazenil (10 mg/kg, i.p.), a benzodiazepine receptor antagonist, reduced the effects of chlordiazepoxide (5 mg/kg, i.p.), but not buspirone (10 mg/kg, i.p.). A combination of the selective beta 1 adrenergic receptor antagonist metoprolol (20 mg/kg, i.p.) and the beta 2 adrenergic receptor antagonist ICI 118,551 (4 mg/kg, i.p.) did not reduce the effects of either buspirone (10 mg/kg, i.p.) or diazepam (1 mg/kg, i.p.). These data show that there are at least two separate routes through which anxiolytic agents reduce the frequency of hippocampal rhythmical slow activity. Buspirone, clonidine, baclofen and 8-OH-DPAT act via a system dependent on 5-hydroxytryptamine 1a receptor activation. Benzodiazepines act via activation of the benzodiazepine receptor and probably share with barbiturates action at the GABA-benzodiazepine-chloride ionophore complex but do not produce their effects, directly or indirectly, by 5-hydroxytryptamine 1a receptor activation.
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Department of Psychology, University of Otago, Dunedin, New Zealand.
McNaughton
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Scott
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000654:Amobarbital / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002707:Chlordiazepoxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003000:Clonidine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004558:Electric Stimulation; D004566:Electrodes; D004569:Electroencephalography / Q000187:drug effects*; D005442:Flumazenil / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D010869:Pindolol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013764:Tetrahydronaphthalenes / Q000037:antagonists & inhibitors / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D013764:Tetrahydronaphthalenes; D005442:Flumazenil; D002707:Chlordiazepoxide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D010869:Pindolol; D000654:Amobarbital; D001418:Baclofen; D003000:Clonidine