PS V – 8

Transdermal delivery of a buprenorphine/naltrexone

combination for the treatment of polydrug abuse

Alistair Taverner, Sarah Cordery, Stephen M. Husbands, Richard H. Guy,Begoña M. Delgado-Charro, Chris P. Bailey

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Background and Aim: There is evidence that a bu-

prenorphine/naltrexone combination may be effective

as a relapse prevention not only for opioid abuse, but

for polydrug abuse, yet little work has been carried

out to determine the optimum ratio of the two drugs.

A significant problem with this treatment strategy

arises from the fact that buprenorphine and naltrexone

need to be administered by different routes. However,

both buprenorphine and naltrexone can be delivered

transdermally using iontophoresis, and we are cur-

rently using this technique to develop a buprenor-

phine/naltrexone combination therapy that is effective

in reducing relapse to polydrug abuse.

Method: Using conditioned place preference (CPP)

in male Sprague-Dawley rats, the rewarding proper-

ties of buprenorphine and naltrexone combinations

were assessed. The ability of buprenorphine/naltrex-

one to inhibit drug-primed reinstatement of morphine-

induced CPP was then tested.

Results: Buprenorphine alone (0.3 mg/kg) was re-

warding, whereas a buprenorphine to naltrexone ratio

of 1:10 (0.3 and 3 mg/kg) was aversive. However,

a ratio of 1:3 (0.3 and 1 mg/kg) was neither rewarding

nor aversive. A morphine priming dose of 2.5 mg/kg

reinstated morphine CPP (animals were trained to

demonstrate CPP with 10 mg/kg morphine followed

by extinction training), an effect that was inhibited by

prior administration of buprenorphine/naltrexone (0.3

and 1 mg/kg respectively). All drugs were adminis-

tered ip

Conclusions: We have demonstrated a combination

of buprenorphine/naltrexone with no rewarding or

aversive effects that appears to inhibit reinstatement

in an animal model of drug-seeking behavior. Ongo-

ing work is designed to further test the ability of

buprenorphine/naltrexone to prevent CPP reinstate-

ment, and to optimise conditions for their transdermal

delivery.

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PS V – 9

Role of the corticotropin-releasing factor receptor-1 in the

conditioned preference place induced by morphine in mice

Carmen Lasheras1, Ana González-Cuello2, Maria Victoria Milanés1, Maria Luisa Laorden1

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Background and Aim: Corticotropin-releasing fac-

tor (CRF) plays a major role in regulating behavioural

and hormonal responses to stress in animal models. It

has been proposed that CRF system contribute in an

important way at compulsive drug use. The purpose of

the present work is to evaluate the ability of the selec-

tive CRF1 receptor (CRF1R) antagonist, CP154,526,

in the conditioned preference place (CPP) induced by

morphine in male mice.

Methods: The rewarding effects of morphine were

evaluated using the CPP paradigm. We gave a dose of

CRF1R antagonist 30 minutes before morphine or sa-

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