Effects of repeated morphine treatment on metabolism of cerebral dopamine and serotonin in alcohol-preferring AA and alcohol-avoiding ANA rats

activity of AA rats, more than that of ANA or non-selected Wistar rats, and, furthermore, AA, but not ANA or Wistar rats, show sensitization to this locomotor-activating effect of morphine by the fourth day of repeated treatment with a 1 mg/kg dose of morphine (Honkanen et al., 1999b). Given that psychomotor stimulation seems to be associated with the reinforcing effects of drugs of abuse (for a review, see Wise and Bozarth, 1987), these results suggest that the reinforcing effects of opioids may be stronger in AA than ANA rats and raises the possibility that properties of the endogenous opioid system may play a role in the differential alcohol consumption behaviours of these rats. This is in line with the suggestion that the endogenous opioid system and regulation of brain dopaminergic mechanisms by opioids play a role in alcohol addiction (Herz, 1997). Thus, the differential effects of opioids on brain dopaminergic systems in AA and ANA rats might be involved in the difference between the alcohol consumptions of these rats. We have previously found that the effect of acute morphine administration on mesolimbic DA release does not differ between AA and ANA rats, whereas the nigrostriatal DA system seems to be more sensitive to morphine in AA rats than in ANA rats (Honkanen et al., 1999a). Thus, in the present study, we wanted to clarify whether synaptic DA release or metabolism is involved in the differential behavioural sensitization induced by morphine in AA and ANA rats. We studied whether repeated morphine pretreatment induces sensitization of DA systems to acute morphine in AA and ANA rats. We measured concentrations of DA and its metabolites, 3-methoxytyramine (3-MT) and homovanillic acid (HVA), in the nucleus accumbens, caudate-putamen and olfactory tubercle of AA and ANA rats after acute or repeated morphine treatment. To prevent the post-mortem changes in the concentration of DA and its metabolites, the rats were killed by head-focused microwave irradiation.