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While it is common to administer lipid\u2010based formulations of \u0394\u20109\u2010THC in human studies orally, intraperitoneal injections of water\u2010based solutions are used in animal models. Because of the poor water solubility of \u0394\u20109\u2010THC, solubilizers such as ethanol and\/or emulsifiers are needed for these preparations. In order to test whether a lipid\u2010based solvent would be superior over a water\u2010based vehicle in rats, we compared the effects on locomotor activity and prepulse inhibition (PPI) of the acoustic startle reaction, as well as pharmacokinetic data obtained from rats' serum and brain tissue samples. Up to 50\u00a0mg\/kg \u0394\u20109\u2010THC in the lipid\u2010based formulation was not able to induce any behavioral alterations, while already 5\u00a0mg\/kg of the water\u2010based \u0394\u20109\u2010THC preparation significantly reduced locomotor activity. This also induced a small but significant PPI reduction, which was prepulse intensity dependent. Interestingly, the reflexive motor response to the startle stimulus was not affected by the water\u2010based \u0394\u20109\u2010THC solution. Analysis of serum and brain \u0394\u20109\u2010THC levels by high\u2010performance liquid chromatography\/mass spectrometry revealed that although the final concentration reached in the brain was comparable for both pharmaceutical preparations, the water\u2010based formulation achieved a faster kinetic. We, therefore, conclude that the slope of the \u0394\u20109\u2010THC concentration\u2010time curve and the resulting cannabinoid receptor type 1 activation per time unit are responsible for the induction of behavioral alterations.<\/jats:p>","DOI":"10.1111\/adb.12745","type":"journal-article","created":{"date-parts":[[2019,4,2]],"date-time":"2019-04-02T11:00:50Z","timestamp":1554202850000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Different pharmaceutical preparations of \u0394<sup>9<\/sup>\u2010tetrahydrocannabinol differentially affect its behavioral effects in rats"],"prefix":"10.1111","volume":"25","author":[{"given":"Cathrin","family":"Rohleder","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim Heidelberg University  Mannheim Germany"},{"name":"Institute of Radiochemistry and Experimental Molecular Imaging Faculty of Medicine and University Hospital Cologne, University of Cologne  Cologne Germany"},{"name":"Department of Multimodal Imaging Max\u2010Planck\u2010Institute for Neurological Research  Cologne Germany"},{"name":"Brain and Mind Centre The University of Sydney  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Pahlisch","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim Heidelberg University  Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf","family":"Graf","sequence":"additional","affiliation":[{"name":"Department of Multimodal Imaging Max\u2010Planck\u2010Institute for Neurological Research  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"Endepols","sequence":"additional","affiliation":[{"name":"Institute of Radiochemistry and Experimental Molecular Imaging Faculty of Medicine and University Hospital Cologne, University of Cologne  Cologne Germany"},{"name":"Department of Multimodal Imaging Max\u2010Planck\u2010Institute for Neurological Research  Cologne Germany"},{"name":"Department of Nuclear Medicine Faculty of Medicine and University Hospital Cologne, University of Cologne  Cologne Germany"},{"name":"Forschungszentrum J\u00fclich GmbH Institute of Neuroscience and Medicine, Nuclear Chemistry (INM\u20105), Wilhelm\u2010Johnen\u2010Stra\u00dfe  J\u00fclich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8163-195X","authenticated-orcid":false,"given":"F. 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