Autoradiographic mapping of brain 5-HT2A binding sites in P and in AA alcohol-preferring rats

There is considerable evidence for an involvement of serotonergic mechanisms in the control of alcohol consumption. In the present study, an extensive 5-HT2A receptor autoradiographic investigation was carried out in two genetically selected rat strains, P and AA alcohol-preferring rats, respectively, as well as in the corresponding NP and ANA alcohol-nonpreferring rats. The aim was to determine if there is any common pattern in 5-HT2A binding site densities that may illuminate mechanisms of alcohol preference in these animals. For quantitating 5-HT2A binding sites, [3H]ketanserin (2 nM) was used. Nonspecific binding was measured in the presence of methysergide 10(-6) M. Results demonstrated a lower level (from 50 to 70%) of 5-HT2A binding sites in the layer IV of prefrontal cortex, frontal cortex, parietal cortex of P rats compared to NP controls. Similarly, in the claustrum, 5-HT2A binding density of P rats was 50% lower than that of NP rats, although this failed to achieve statistical significance. No difference was detected in the other areas investigated, including the olfactory tubercles, nucleus accumbens, caudate putamen, pyriform cortex, ventral tegmental area, temporal cortex, and entorhinal cortex. In AA rats, [3H]ketanserin binding density measured in these brain areas was very similar to that observed in ANA nonpreferring controls, and statistical analysis did not reveal any significant difference between the two rat lines. The present study confirms previous reports demonstrating lower densities of 5-HT2A binding sites in the P rats and provides the first autoradiographic evidence showing that such an alteration does not occur in AA rats. These findings suggest that the expression of high alcohol preference in genetically selected P and AA rats is not associated with a shared neurochemical alteration of the 5-HT2A receptor system.