Comparison between intraperitoneal and subcutaneous phencyclidine administration in Sprague–Dawley rats: A locomotor activity and gene induction study
| Autor: | Peter R. Maycox, Nigel E. Austin, Melanie J. Robbins, Susan H. Moore, Kevin M. Savage, Declan N.C. Jones, Mikhail Kalinichev, Elizabeth M. Hartfield |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Transcriptional Activation Hallucinogen JUNB Injections Subcutaneous Phencyclidine Prefrontal Cortex Motor Activity Pharmacology Psychoses Substance-Induced Rats Sprague-Dawley Route of administration Pharmacokinetics medicine Animals Genes Immediate-Early Biological Psychiatry Behavior Animal Reverse Transcriptase Polymerase Chain Reaction business.industry Antagonist Brain Rats Disease Models Animal Gene Expression Regulation Schizophrenia NMDA receptor business Immediate early gene Injections Intraperitoneal medicine.drug |
| Zdroj: | Progress in Neuro-Psychopharmacology and Biological Psychiatry. 32:414-422 |
| ISSN: | 0278-5846 |
| DOI: | 10.1016/j.pnpbp.2007.09.008 |
| Popis: | In a putative model of acute phencyclidine (PCP)-induced psychosis we evaluated effects of the drug on locomotor activity (LMA) and immediate early gene (IEG) induction in the rat using two routes of drug administration, intraperitoneal (i.p.) and subcutaneous (s.c.). Adult male rats received saline or PCP (1.0–5.0 mg/kg) either i.p or s.c. and were assessed for LMA for 60 min. At the end of the LMA testing animals were culled and blood and brain samples were collected for PCP concentration analysis. Separate cohorts of animals received 5.0 mg/kg PCP (i.p. or s.c.) and were used to investigate (1) the pharmacokinetics of PCP or (2) induction of IEG (Arc, c- fos , BDNF, junB, Krox-20, sgk-1, NURR1, fra-2, Krox-24, and egr-3) mRNA expression in the prefrontal cortex (PFC). Administration of PCP resulted in locomotor hyperactivity which was more robust and longer-lasting in animals dosed s.c. compared to i.p.-treated-animals. Differences in hyperlocomotion were paralleled by higher concentrations of PCP in the blood and in the brain of s.c.-treated animals compared to i.p.-treated animals. The differences in the concentration of PCP between the two routes of administration were detected 30 min after dosing and persisted for up to 4 h. Administration of PCP via the s.c. route resulted in induction of more IEGs and consistently larger magnitudes of induction than that via the i.p. route. Therefore, we have outlined the dosing conditions to induce rapid and robust effect of acute PCP on behaviour, gene induction, and pharmacokinetic profile, to allow investigation of this as a potential animal model of acute psychosis. |
| Databáze: | OpenAIRE |
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