213 92 92 3 3 S. Hjorth A. Carlsson J. A. Engel Department of Pharmacology University of Göteborg P.O. Box 33031 S-40033 Göteborg Sweden Abstract The effect of the (+)- and (-)-enantiomers of 3-PPP (conventional and atypical dopamine (DA)-receptor active agent, respectively) were investigated in a commonly used animal model of anxiety: the Vogel licking-conflict test. Low doses (≤0.5 mg/kg SC) of both 3-PPP enantiomers resulted in anti-conflict (=anxiolytic-like) actions in this test. (-)-3-PPP proved to be almost as potent as apomorphine in releasing the punished responding (minimum effective doses; (-)-3-PPP: 0.016, and apomorphine: 0.006 mg/kg SC), whereas (+)-3-PPP was about 10 times less effective than apomorphine. In the higher dose range (≥1.0 mg/kg), both 3-PPP enantiomers instead induced an apparent “pro”-conflict effect; i.e. decreased responding to a level significantly below baseline, thus resulting in a biphasic dose-response curve. Simple alterations in the animals' motivation to drink, in shock threshold or in motor capabilities did not seem to be major explanatory factors either for the anti- or for the “pro”-conflict effects. With regard to the latter, the possibility is discussed of an interaction between the experimental test situation and non conflict-related effects of the drugs, thus interfering with the punished drinking. The findings are interpreted within the concept that low doses of the 3-PPP enantiomers, in particular (-)-3-PPP, may attenuate anxiety-elicited increases in the neurotransmission in certain meso-cortical/limbic DA pathways, i.e. consistent with the previously shown preferentially “limbic” net antidopaminergic profile of action of (-)-3-PPP. The results support an active role for DA in conditions associated with anxiety and reinforce the view that novel putative anxiolytics might be found among selective DA-modulating agents like, e.g. the atypical DA receptor agonist (-)-3-PPP.
Psychopharmacology – Springer Journals
Published: Jul 1, 1987
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