Issn Print: 0955-8810
Publication Date: 2005/09/01
A121 EXAMINATION OF CROSS-SENSITIZATION TO COCAINE OR HEROIN FOLLOWING REPEATED EXPOSURE TO NICOTINE
C.E. Green; A.C. Jermyn; S. Monka; F.H. Murray; H.L. Alderson
Excerpt
The development of sensitized responses in the mesocorticolimbic dopamine (DA) system to drugs of abuse following repeated drug exposure is thought to lead to critical changes in associative learning processes that underlie the compulsive nature of drug-taking behaviour in addiction. This can be investigated by examination of the development of behavioural sensitization to the locomotor stimulant effects of a drug following repeated exposure. Behavioural sensitization can be expressed not only in response to the repeated drug, but also to the effects of other drugs – cross-sensitization. Nicotine is a very commonly abused drug, and we wished to investigate the hypothesis that repeated nicotine exposure would produce cross-sensitization to other drugs of abuse, namely cocaine and heroin. Rats were treated with either nicotine (0.4 mg/kg) or phosphate buffer (PB) vehicle on seven occasions, separated by 48 h. After nicotine treatment was a challenge day, on which rats received either cocaine (10 mg/kg), heroin (0.5 mg/kg) or PB. Locomotion following each drug treatment was examined during a 60 min session. Nicotine initially depressed locomotor activity, but induced locomotor activation from session 4 onwards, which became sensitized over the remaining sessions. On the challenge day, rats that had been pre-treated with nicotine showed significantly higher levels of locomotion in response to heroin challenge than those pre-treated with PB. In contrast, pre-treatment with nicotine did not significantly enhance the locomotor response to cocaine challenge. These results indicate that cross-sensitization between developed nicotine and heroin, but not between nicotine and cocaine. This difference in cross-sensitization may be the result of the different ways in which nicotine and cocaine have their effects on the mesocorticolimbic DA system, in comparison with the more similar mechanisms underlying the actions of nicotine and heroin.
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