Figure 4.

Animals that are supersensitive to dopamine‐like drugs (e.g., apomorphine, cocaine, methylphenidate, amphetamine) reveal elevated proportions of dopamine D2 receptors that are in the high‐affinity state for dopamine, D2^High (left). The data summarized here were obtained on striata from animals found to be dopamine supersensitive under the following conditions (listed from the upper left top down; unless otherwise specified, details are found in [36, 38]: Mature rats with neonatal lesion of the hippocampus [46]. Rats sensitized by long‐term treatment with amphetamine. Rats socially isolated after weaning [40]. Knockouts of GABA B1(–/–) receptors in mice (B. Bettler and P. Seeman, unpublished). Knockouts of metabotropic glutamate mGlu3 receptors in mice [39]. Knockouts of metabotropic glutamate mGlu2 receptors in mice [39]. Five days of 10 mg/kg corticosterone treatment to rats. Knockouts of the DBH (dopamine‐beta hydroxylase) gene in mice. Long‐term ethanol treatment of rats [47]. Rats sensitized to phencyclidine. Rats treated for 14 days with cannabinoid HU210 at 20 μg/kg (Moreno et al., 2005; F.J. Bermudez Silva, F. Rodriguez de Fonseca, J. Suarez, and P. Seeman, unpublished). Knockouts of trace amine‐1 receptors in mice [48]. Rats sensitized by long‐term treatment with methamphetamine [49]. Rats sensitized and addicted by long‐term self‐treatment with cocaine [50]. Knockouts of the RGS9–2 (regulator of G protein signaling‐9) gene in mice. Knockouts of the dopamine D4 receptor gene in mice. Knockouts of the GPRK6 (G protein‐coupled receptor kinase) gene in mice. Cholinergic lesion in the cerebral cortex of rats. Long‐term high‐dose treatment of rats with caffeine [51]. Mice made dopamine‐deficient by tyrosine hydroxylase knockouts. Knockouts of alpha‐1b‐adrenoceptors in mice [52]. Rats with entorhinal lesions of the hippocampus [53]. Knockouts of PSD95 (postsynaptic density 95) gene in mice (M. Beaulieu, M. Caron, and P. Seeman, unpublished). Rats born by Caesarian section with anoxia. Rats treated with reserpine (5 mg/kg for 3 days; 2 days no drug). Mice with COMT (catechol‐O‐methyl transferase) gene knockouts. Rats with neonatal lesion of the hippocampus [54]. Rats treated with cannabinoid WIN 55,212–2 (4 mg/day for 14 days; F.J. Bermudez Silva, F. Rodriguez de Fonseca, J. Suarez, and P. Seeman, unpublished). Rats spontaneously active and explorative (no treatment)[55]. Mice with knockouts of dopamine transporter DAT or vesicle monoamine transporter‐2 VMAT‐2 [56]. Rats sensitized to quinpirole. Mice with knockouts of RIIbeta protein kinase A. The right side [36, 38] shows either the lack of elevation, a minor elevation, or an actual fall in the proportion of D2^High receptors in mice with knockouts in the genes for glycogen synthase kinase (GSK3beta), metabotropic glutamate receptor mGluR5, dopamine D1 or D3 receptors, histamine H1, H2 or H3 receptors, and adenosine A2A receptors. Nine days of ketanserin treatment also had no effect on D2^High receptors. (Adapted and extended from [38]; with permission from Wiley & Sons, Inc.; Reproduced from [31] with permission from Walsh Medical Media LLC).