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Groups of rats received once daily subcutaneous treatments for 22 days with haloperidol (0.5 mg/kg), clozapine (20 mg/kg), SCH 23390 (0.2 mg/kg) or vehicle. Quantitative immunoblots for Gi alpha 1, Gi alpha 2, G(o alpha), Gs alpha (45 kD), G beta 35 and G beta 36 were performed on membranes from the following brain regions: striatum, nucleus accumbens, substantia nigra, ventral tegmental area (VTA), prefrontal cortex and hippocampus (CA1). No significant alterations were found in the levels of any of these G protein subunits, in any brain region in treated vs control rats.

Treatment of rats with the peptide coupling agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (6 mg/kg i.p.) irreversibly reduced the binding of [3H]spiperone ([3H]SPIP) and cis-[3H] piflutixol to striatal D2 and D1 receptors, respectively, by 70 to 75%. In each instance only the receptor density was affected, without a change in the dissociation constant (Kd) of either radioligand. Pretreatment with sulpiride (200 mg/kg i.p.), a selective D2 antagonist, preferentially protected [3H]SPIP sites against N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline-induced inactivation, whereas pretreatment with SCH 23390 (3 mg/kg i.p.), a putative selective D1 antagonist, preferentially blocked the inactivation of cis-[3H]piflutixol binding sites. N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline markedly reduced radioligand binding to cortical alpha-1 ([3H]prazosin) and alpha-2 [( 3H]yohimbine) receptors (10-20% of control) but had a lesser effect on serotonin-2 ([3H]SPIP) and serotonin-1 ([3H]5-HT) receptors (30-40% of control). Muscarinic cholinergic ([3H] quinuclidinyl benzilate) and beta adrenergic ([3H]dihydroalprenolol) receptors were only slightly affected. None of these nondopaminergic sites were protected by sulpiride or SCH 23390, with the exception of serotonin-2 and serotonin-1 which were partially protected by the latter. SPIP (0.2 mg/kg i.p.), haloperidol (1 mg/kg i.p.) and pimozide (2 mg/kg i.p.) all selectively protected the D2 receptor, whereas cis-flupenthixol (2 mg/kg i.p.) protected both dopamine receptors; its inactive isomer trans-flupenthixol (20 mg/kg i.p.) protected neither. Bulbocapnine (25 mg/kg s.c.) selectively, but partially, protected the D1 site.(ABSTRACT TRUNCATED AT 250 WORDS)