vocalization and jump/flinch behaviours in a grid stim apparatusdelivering electrical stimulation through a grid floor. A secondaryobjective was to investigate whether the plasma levels of morphineand its mainmetabolite (morphine-3-glucuronide, M3G) was affectedafter chronic treatment (15 months) with THC. Pre-treatment withTHC for 13 days did not change the antinociceptive potency ofintravenous administration of morphine. However, the plasma con-centrations of morphine and M3G appeared to be higher in chronicTHC treated rats than in naïve rats. The nociceptive response in theseanimals has not yet been investigated. Thus, the present study didnot indicate any antinociceptive potentiation or cross-tolerance aftersubchronic THC and acute morphine treatments in rats.

doi:10.1016/j.vascn.2010.11.104

Poster Number: 101Board Number: 40

Evaluationof the effects of fluoxetine dependencyon cardiovascularand withdrawal parameters in ratsPhilip R. Atterson, Cindy Roegge, John Yohe, Kasey Landis

WIL Research Laboratories, LLC, Ashland, OH, United States

The aim of this investigation was to assess changes in autonomicfunction during the development of addiction to the SSRI fluoxetine(FLX) and the subsequent withdrawal (WD) period. Groups of 8Sprague Dawley rats (4/sex), implanted with radiotelemetry trans-mitters, received either deionized water or FLX over a 21 day periodwith weekly increases in FLX doses resulting in 7.5, 15 and 20 mg/ kgBID, respectively. Blood pressure (systolic, diastolic, mean), pulsepressure, heart rate (HR), body temperature and motor activity werecollected every 3 h prior to and during dosing, and during the 15 dayspontaneous WD period. Food consumption (FC) and body weight(BW) were recorded daily. The WD period for males was shortened to5 days due to mortality in the FLX males. Reductions in BW and FCwere noted in the FLX rats during treatment and the early WD period,but BW gain in the FLX females displayed similarity to controls bythe end of the WD period due to increased FC after 4 days of WD.Decreased HR and increased blood pressures were noted in the FLXrats during the treatment and WD phases, with rebound decreasesin blood pressures being noted in the FLX females starting after6 days of WD. Decreased body temperature and motor activity wereobserved in FLX males. Clinical observations of WD in the FLX ratsincluded twitches/tremors, ataxia/posture changes, piloerection,tail erection and initial weight loss. The results of this study showthat the effects of FLX dependency and WD include alterations incardiovascular function, appetite and behavior.

doi:10.1016/j.vascn.2010.11.105

Poster Number: 102Board Number: 41

Strain dependent differences in operant self-administrationof cocaineClare E. Flint

Covance Laboratories Ltd., Harrogate, North Yorkshire, England

The operant self-administration paradigm provides an assess-ment of the abuse liability of psychoactive compounds, and may be

used to investigate the potential of new chemical entities to exhibitreinforcing effects. Lister Hooded (LH) rats have routinely been usedfor behavioural research; yet many toxicology programmes arecarried out in Sprague-Dawley (SD) or Han Wistar (HW) rats. Toexplore the possibility of using either strain, we performed acomparative study. In our laboratory we compared the self admin-istration of cocaine via surgically implanted venous cannulae in LH,SD and HW rats. Following a period of post-surgery recovery, animalswere placed in operant chambers for a two hour daily session, wherethey had access to two levers, one of which provided an infusion ofcocaine (0.1 mg/infusion). Initially training commenced under aFixed Ratio 1 schedule (FR1), and when stable responding wasestablished, progressed to a FR3 schedule, and ultimately to an FR10schedule. Following 10 training sessions, 90% of LH rats wereconsidered positive responders on a FR10 schedule and were readyfor stable response testing, with a mean of 36±12.6 infusions peranimal and 92%±6.36 drug-paired lever presses in the tenth 2 hoursession. HW and SD rats had not progressed beyond a FR1 schedule,and none of the rats were exhibiting stable responding. After afurther 11 days training, one SD rat was deemed ready for stableresponse testing. In conclusion, LH rats were quicker to reach stableresponding, and would therefore be the strain of choice for futurestudies.

doi:10.1016/j.vascn.2010.11.106

Poster Number: 103Board Number: 42

Evaluation of chlordiazepoxide withdrawal effectsusing telemetryPaul Moser, Christelle Froger-Colleaux, Vincent Castagn,Olivier Pouessel, Sonia Rompion

Porsolt & Partners Pharmacology, Boulogne-Billancourt, France

The procedures used to assess spontaneous withdrawal effectsneed to be sensitive and widely applicable, i.e. not specific to anyparticular drug class, and the measures used should not be affectedby repeat testing. For these reasons we have concentrated ondeveloping sensitive somatic measures of withdrawal effects andhave previously described the withdrawal effects of morphine after20 days of treatment using telemetry to continuously follow bodytemperature, blood pressure, heart rate and motor activity in additionto food intake and body weight gain. We now report on the effects of20 days of treatment with chlordiazepoxide (CDP; 16, 32 or 64 mg/kgp.o. b.i.d.) and 8 days withdrawal in Wistar rats. The results show thatchronic CDP slightly increased food intake and body weight gain, aswell as disrupting the normal circadian patterns of body temperature,motor activity, blood pressure and heart rate, although most of theseeffects tolerated out within 10 days. Following withdrawal, all groupsof CDP-treated rats showed a marked decrease in food intake and lossof weight which were maximal on day 2 of withdrawal. There wasalso an increase in diurnal measures of body temperature (~+0.5 °C),blood pressure (~+10 mmHg), heart rate (~+50 bpm) and locomo-tor activity onday 1 ofwithdrawal. The intensityandduration of effectswere broadly dose-related. All parameters had returned to normalbyday 8 ofwithdrawal. These data further support the use of telemetryto monitor withdrawal effects.

doi:10.1016/j.vascn.2010.11.107

Abstracts e31