/ eh10 5029 Mp 163 Wednesday Jun 11 06:49 AM EL–PB (v. 62,no.1) 5029 163 Physiology & Behavior, Vol. 62, No. 1, pp. 163 – 167, 1997 Copyright q 1997 Elsevier Science Inc. Printed in the USA. All rights reserved 0031-9384/97 $17.00 / .00 PII S0031-9384( 97 ) 00029-2 A Novel Chronic and Detachable Indwelling Jugular Catheterization Procedure for Mice BRIAN M.KELLEY, 1 ANGELA-LEIGH E. BANDY AND LAWRENCE D. MIDDAUGH Center for Drug and Alcohol Programs ( CDAP ) , Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425-0742 USA Received 7 November 1996; Accepted 5 February 1997 KELLEY,B. M.,A. E. BANDY AND L.D. MIDDAUGH. A novel chronic and detachable indwelling jugular catheterization procedure for mice. PHYSIOL BEHAV. 62 ( 1 ) 163 – 167, 1997. — The purpose of this study was to describe and demonstrate the usefulness of a chronic, detachable, indwelling jugular catheterization apparatus in mice that can be applied to acute or chronic IV drug administration in freely moving, unrestrained mice. The application of this procedure to the study of abused drugs is particularly advantageous, because the commonly employed intraperitoneal ( IP ) , SC,and per os ( PO ) routes of administration fail to mimic the near complete and instantaneous bioavailability of drugs abused by IV injection or inhalation ( e.g., cocaine ) . Compared to current IV administration methods, the detachable catheter system presented in this paper is relatively easy to construct, simple to use, and appears to remain patent for an extended period of time. In addition, the utility of this procedure is greatly increased because the subject does not have to remain permanently attached to a complicated tether system. Thus, the tes subject can be infused with a drug, detached from the catheter, and then undergo some behavioral test that would otherwise be impossible to undergo with a tethered system. For the purposes of demonstrating catheter patency and the importance of an IV route of administration, a conditioned place preference ( CPP ) paradigm was used to evaluate the reinforcing efficacy of co- caine. q 1997 Elsevier Science Inc. Intravenous self-administration Cocaine C57 mouse Indwelling catheter Conditioned place preference 1 To whom requests for reprints should be addressed. E-mail:kelleyb@musc.edu FOR an effective animal modelof drug abuse, the route of administration should allow the drug’s pharmacokinetic pro- file to closely match that in humans. This interspecies simi- larity is particularly important in animal models of the rein- forcing efficacy and / or addictive potential of abused drugs. The SC and IP routes of administration frequently used in rodentdrug abuse research fail to mimic the rapid bioavail- ability observed with IV administration. Furthermore, SC and IP routes are subject to ‘‘first pass’’ metabolism via the hepatic portalcirculation, which can result in inconsistent bioavail- ability. With the IV route of administration, complete and near instantaneous distribution of the drug is possible. The devel- opment and application of an IV mouse model is particularly advantageous ( i.e., compared to rat models ) considering the tremendous variety of ‘‘knock-out’’ mice and mouse strains currently available. Several models for IV administration of drugs to mice have been offered ( 1,2,5,6 ) ; however, each has several problems. For example, each ofthe methods employed a complicated tethered-catheter system that can extend more than 35 cm in length from the subject’s dorsal incision and, in some cases, the catheter is anchored to the subject’s skull with dental ce- ment. Such a system increases the complexity of the surgery; it increases the time the subject is in surgery, and increases the likelihood that infection will develop. Because the mouse is always attached to this lengthy tether, nothing can extend into the subject’s home cage ( e.g., sipper tubes or feeders ) and a complicated and sometimes expensive mobile swivel unit is required. Furthermore, to change the drug that is being infused,the entire catheter must firstbe flushed. To inhibit bacterial growth within the catheter, it mustbe flushed with antibiotics between periods of use. Finally,the range of be- havioraltesting procedures and / ormeasures( e.g.,water maze,open field, running wheel, etc.) are greatly restricted because the subject mustremain permanently attached to its tether. These problems motivated us to develop a chronic, de- tachable ( i.e., nontethered ) , indwelling jugular catheteriza- tion apparatus for mice. The design of our detachable catheter apparatus is simpler to construct, easier to use, less costly, and allows for a greater variety of behavioral measures. Although the purpose of this paper was to illustrate a novel methodology for a chronic detachable indwelling jugular catheter in mice, a conditioned place preference ( CPP ) paradigm was utilized to demonstrate the patency of the catheter and the importance