Dopamine receptor sub-types involvement in nucleus accumbens and ventral tegmentum but not in medial prefrontal cortex: on self-stimulation of lateral hypothalamus and ventral mesencephalon

Abstract

The involvement of different sub-types of dopamine receptors in the electrical self-stimulation behaviour was investigated using DA receptor subtype specific agonists viz R(+) SKF 38393 and LY 171555 (quinipirole). Rats were chronically implanted with bipolar electrodes in lateral hypothalamus-medial forebrain bundles (LH-MFB) and ventral tegmental area-substantia nigra (VTA-SN) or guide cannula in nucleus accumbens (nACB) or medial prefrontal cortex (mPFRCx) or cannula-cum-electrode in VTA-SN. Combining these, it was possible to inject a given receptor ligand in either nACB or mPFRCx or VTA-SN and assess the changes in intracranial self-stimulation (ICSS) of LH-MFB or VTA-SN. The experimental subjects were trained to press a pedal to obtain 0.25 s trains of cathodal rectangular pulses of 0.1 ms pulse duration (for LH-MFB electrode) or 0.3 ms pulse duration (for VTA-SN electrode). The rate-frequency curve for each subject and each placement were obtained in order to determine M 50 (50% of maximum asymptotic response rate). Microinjection of SKF 38393 (a D 1 agonist) or LY 171555 (a D 2 agonist) into nACB caused facilitatory and suppressive effects on the ICSS of VTA-SN and LH-MFB respectively. On the contrary, intra VTA-SN injection of 10 μg/0.5 μl of SKF 38393 or of LY 171555, reduced its ICSS to half as compared to vehicle injections. Under the effect of these injections, there was no change in the ICSS of LH-MFB. The combined administration of SKF 38393 (5 μg) and LY 171555(10 μg) into nACB produced suppression of ICSS of VTA-SN to greater extent than the LY 171555 (10 μg/0.5 μl). This indictes that coactivation of D 1 and D 2 leads to suppression of ICSS of VTA-SN. The activation of D 1 receptors in nACB facilitates the ICSS of both VTA-SN and LH-MFB by increasing the reinforcement and/locomotor activity, while the activation of D 2 receptors in it has opposite effect. The coactivation of D 1 and D 2 receptors in VTA-SN leads to the suppression of ICSS of both VTA-SN and LH-MFB. Similar injections of these receptor ligands into mPFRCx did not alter the ICSS of either LH-MFB or VTA-SN. The pre- or post-synaptic DA receptors of mPFRCx do not appear to influence the ICSS of either VTA-SN or LH-MFB in any significant manner.