Drug discrimination in pentylenetetrazol‐trained baboons: Generalization to buspirone and β‐carboline‐3‐carboxylic acid ethyl ester but not lorazepam or pentobarbital

Research output: Contribution to journalArticlepeer-review

Abstract

Pentylenetetrazol (PTZ) has been characterized as producing anxiogenic effects in humans and rats, and PTZ drug discrimination procedures in rats have been used to categorize drug effects as anxiogenic. In the present study, baboons trained to discriminate a subconvulsant dose of PTZ from the no‐drug condition showed dose‐dependent generalization to PTZ and to β‐carboline‐3‐carboxylic acid ethyl esther [β‐CCE; a benzodiazepine (BZ)‐receptor inverse agonist] but no generalization to the BZ‐receptor antagonist Ro 15‐1788 (flumazenil). Ro‐1788 produced surmountable antagonism of the β‐CCE discriminative stimulus. The novel anxiolytic buspirone also occasioned 100% drug lever responding in the PTZ‐trained baboons, although lorazepam and pentobarbital did not. Results with the 5HT ligand 8‐hydroxy‐2‐(di‐n‐propylamino)tetralin (8‐OH‐DPAT) were mixed. Lorazepam but not buspirone antagonized PTZ. Observations of baboons after PTZ, buspirone, and β‐CCE at doses occasioning PTZ lever responding showed that tremors and agitation occurred after buspirone but not after β‐CCE or PTZ.

Original languageEnglish (US)
Pages (from-to)257-267
Number of pages11
JournalDrug Development Research
Volume16
Issue number2-4
DOIs
StatePublished - 1989

Keywords

  • 8‐OH‐DPAT
  • Ro‐15‐1788
  • anxiety
  • flumazenil

ASJC Scopus subject areas

  • Drug Discovery

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