The Effect of Striatum and Brain Activity by D2 and D2 Dopamine-Receptor Antagonists
The striatum together with other parts of the basal ganglia form direct and indirect pathways (mesolimbic, mesocortical, nigrostriatal and tuberoinfundibular pathways), that are modulators of activities through disinhibition. Co-activation of the direct pathway through the Substantia Nigra/ Globus Pallidus Interna (GPi/SNr) and the indirect pathway through the Globus and Subthalamic nucleus (STN) facilitate action selection in a balanced saccade which subvert normal functions of cognition, motivation, pleasure behavior and fine motor control as well as extrapyramidal activity (M, SW, C, & MG., 1996).
The experience of reward is a function of the activation of the mesolimbic pathway such that overstimulation by postsynaptic dopamine recruitment leads to hallucinations and delusions (Adinoff, 2004). However, blocking postsynaptic D2 and D3 receptors by antagonists such as haloperidol in the striatum and ventral tegmental area interferes with the dopamine pathways to the brain regions in animal models and possibly humans than atypical antipsychotics (Xiberas, et al., 2001). This partly explains why patients on these medications experience the relief of positive schizophrenic symptoms.
The common D2 receptor antagonists which are majorly metoclopramide and antipsychotic drugs such as amisulpride, phenothiazines (Chlorpromazine, thioridazine) and thioxanthenes (flupenthixol) as well as Butyrophenones (Haloperidol, droperidol) block the D2 and D3 receptors. Blocking postsynaptic D3/D2 receptors in the ventral tegmental area reduce dopaminergic concentrations in the projections to the nucleus accumbens that form the reward pathway. This is probably responsible for the antipsychotic effect and reduction of positive symptoms of schizophrenia observed in patients who were on high dose amisulpride (Allan J. Coukell, 1996).According to (Kahnt, Weber, Haker, Robbins, & Tobler, 2015), the administration of amisulpride a D2 antagonist facilitated enhanced decoding in the prefrontal and motor cortices indicating that D2 blockade favors GABAergic inhibition.
This is consistent with research carried out by (Waters, Svensson, Haadsma-Svensson, et al. 1993) which demonstrated that a compound U99194A could antagonistically bind to a section of D3 postsynaptic dopamine receptors that caused suppression of some psychomotor activity of rats which is consistent with the hypothesis that blocking striatal post synaptic D3 and majorly D2 receptors is accompanied by presynaptic antagonism as well. Other previous findings from studies such as done by (M, SW, C, & MG., 1996 and Beaulieu & Gainetdinov, 2011 propose findings that show the effect of antagonists binding to D2 and the recent D3 receptors cause deficiencies in the mesocortical pathway functions as demonstrated by the emotion, affect and cognition functions alteration of the prefrontal cortex following administration of antipsychotic medicines.ConclusionFrom the above research it is evident that the dopaminergic activities in the striatum and mesolimbic pathway decrease following binding of antagonists to postsynaptic D2 and D3 receptors. This is because, as demonstrated above the neurons in the reward pathway from the ventral tegmental area to the nucleus accumbens, amygdala as well as other forebrain regions requires dopamine as the primary neurotransmitter to elicit impulses that drive motivation, emotion and reward.
References
Adinoff, …
