Molecular Neurobiology of Dopaminergic Receptors

Repeated Cocaine Administration Induces Gene Expression Changes through the Dopamine D1 Receptors

“…The DA D1 receptor is expressed in multiple brain regions, including the CPu and NAc, areas that mediate the effects of cocaine (Civelli et al, 1993;Gingrich and Caron, 1993;Sibley et al, 1993;Missale et al, 1998). The D1 receptor interacts with G s proteins, and stimulation of the receptor leads to increased intracellular levels of cAMP, resulting in the activation of a transcription factor, the cAMP-response element binding protein (CREB; Civelli et al, 1993;Gingrich and Caron, 1993;Sibley et al, 1993;Missale et al, 1998).…”

“…The D1 receptor interacts with G s proteins, and stimulation of the receptor leads to increased intracellular levels of cAMP, resulting in the activation of a transcription factor, the cAMP-response element binding protein (CREB; Civelli et al, 1993;Gingrich and Caron, 1993;Sibley et al, 1993;Missale et al, 1998). Activated CREB can regulate the expression of cellular genes including the immediate-early gene (IEG) c-fos (Nestler, 2000(Nestler, , 2001.…”

Early expression of D3dopamine receptors in murine embryonic development

“…Two categories of dopamine receptor are currently recognised, termed D1 and D21, the latter in particular being associated with a number of neuropathological conditions (reviewed in [2]). While it is generally accepted that the cloned D2, D3 and D4 subtypes are of the D2 type, their differential roles in brain function remain to be determined [3,4]. A further level of diversity is found in the D2 subclass by the presence of alternative splicing in the D2 and D3 subtypes, generating long and short isoforms of each receptor, termed D2L, D2s, D3L and D3s [5][6][7][8], but the significance of alternative splicing to receptor function is still not clear.…”

Increased desensitization of dopamine D2 receptor-mediated response in the ventral tegmental area in the absence of adenosine A2A receptors

“…D 2 receptor desensitisation is not normally apparent when agonists are used to inhibit dopamine neuron firing in vitro (Fig. 1) (Bowery et al, 1994;Mercuri et al, 1997;Centonze et al, 2002) or in vivo (Bunney et al, 1973;White & Wang, 1984;Kalivas et al, 1993;Sibley et al, 1993;Adell & Artigas, 2004), in agreement with their role of providing essential feedback autoinhibition on dopamine neurons. However, desensitisation can be induced with high concentrations of agonists (Beckstead & Williams, 2007), in particular with accumulative dosing (Fig.…”

“…In addition, the VTA is suggested to be the site important for the development of sensitization to repeated exposures to drugs of abuse, via effects of dopamine on dopamine receptors (Wise, 1996) and neuroplastic changes at glutamatergic synapses (Bonci & Malenka, 1999 (Bouthenet et al, 1987;Wamsley et al, 1989;Chen et al, 1991;Adell & Artigas, 2004), where activation of D 2 receptors inhibits the firing activity of dopamine neurons, carrying out an important autoinhibitory function (Bunney et al, 1973;White & Wang, 1984;Sibley et al, 1993;Mercuri et al, 1997;Adell & Artigas, 2004). …”