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Di-n-propylacetate-induced abstinence behaviour as a possible correlate of increased GABA-ergic activity in the rat

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Abstract

Administration of di-n-propylacetate (DPA), an inhibitor of SSA-dehydrogenase, produces in naive rats abstinence behaviour which can be blocked by morphine and bicuculline and may be useful as a behavioural correlate of increased GABA-ergic activity. The usefulness of this model has been demonstrated by studying the effec of bicuculline, picrotoxin, strychnine, morphine, aminooxyacetic acid, 3-mercaptopropionate and thiosemicarbazide on DPA-induced abstinence behaviour. Behaviour was suppressed both by bicuculline or picrotoxin, while the selective glycine antagonist strychnine was ineffective. A comparable syndrome could not be evoked by treatment with aminooxyacetic acid, a GABA-transaminase inhibitor, indicating that the effect of DPA was not caused by inhibition of this enzyme. Instead, aminooxyacetic acid suppressed the DPA-induced abstinence behaviour, suggesting that two GABA-ergic systems with opposite effects on behaviour can be distinguished. The syndrome was also suppressed by convulsant doses of 3-mercaptopropionate, while thiosemicarbazide was ineffective. Abstinence behaviour was further suppressed by morphine with an ED50 of 0.5 mg/kg and this action could be clearly separated from its depressant effect on locomotor activity in non-treated animals. These results suggest that morphine receptors may be involved in DPA-induced abstinence behaviour. Based on these experiments a model has been proposed for GABA-ergic terminals being under the inhibitory influence of GABA-ergic autoreceptors. It is proposed that DPA-induced abstinence behaviour may be useful as a model of increased GABA-ergic activity to aid study of the regulation and properties of the GABA-ergic system in vivo.

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  1. Th. de Boer

    Present address: Dept. of Pharmacology and Neurology, Medical Faculty Free University, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands

Authors and Affiliations

  1. Department of Pharmacology, Erasmus University Rotterdam, P.O.Box 1738, Rotterdam, The Netherlands

    Th. de Boer, K. Bartels, H. J. Metselaar & J. Bruinvels

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de Boer, T., Bartels, K., Metselaar, H.J. et al. Di-n-propylacetate-induced abstinence behaviour as a possible correlate of increased GABA-ergic activity in the rat. Psychopharmacology 71, 257–267 (1980). https://doi.org/10.1007/BF00433060

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