Neophobia and cortical and subcortical binding of the dopamine D 2 receptor antagonist [ 3H]-raclopride

Abstract

The potential role of dopamine system in response to novelty was analysed using the selective dopamine D 2 receptor antagonist, raclopride, in behavioral and biochemical assays, in rats (the open field test, and specific binding of [ 3H]-raclopride, within different brain structures measured with autoradiography). It was found that raclopride at a low dose (50 μg/kg, IP) caused anxiolytic-like effect (increased the anti-thigmotactic index), whereas at a higher dose (500 μg/kg, IP) produced general inhibitory influence, and decreased the anti-thigmotactic index. Analysis of the behavioral and biochemical results of the experiment revealed a significant negative correlation between the ligand binding in the substantia nigra pars reticulata (SNR), and the number of entries into the central sector of the open field (r = −0.48, p < 0.05), as well as the positive correlation between time spent in the central sector of the open field and [ 3H]-raclopride binding within nucleus accumbens septi (r = 0.57, p < 0.05). Factor analysis revealed a Factor 1 (eigenvalue = 3.361) grouping parameters of central entries into the open field and [ 3H]-raclopride binding in the SNR (factor loadings are 0.814 and 0.703 respectively), indicating that both phenomena are under control of a similar central process. The above data are discussed in relation to the structure dependent dopamine D 2 receptor mechanisms in a rat response to novelty.