Spiroperidol binding

Trulson, ME., and Ulissey. J.J. Chronic cocaine administration decreases dopamine synthesis rate and increases [ H] spiroperidol binding in rat brain. Brain Res Bull 19 35-38, 1987. 

Robertson, H. A. (1982) Chronic phencyclidine, like amphetamine, produces a decrease in (3H)spiroperidol binding in rat striatum. Eur. J. Pharmacol., 78 363-365. 

The effects of developmental exposure of pyrethroids on the dopaminergic system, which is considered to be related to behavior, were examined in several studies, but inconsistent results were obtained. Administration of deltamethrin between gestation day 6 and 15 induced increase of DOPAC (dopamine metabolite) levels in adult rats [54]. Exposure of fenvalerate on gestation day 18 and during postnatal days 2-5 produced no effect on monoamine levels on postnatal day 21 [55]. Gestational and lactational exposure to fenvalerate decreased and increased 3H-spiroperidol binding in striatum after development, respectively, whereas only lactational exposure of cypermethrin induced increase in 3H-spiroperidol binding [56]. 

For each response examined, inhibition of isoproterenol-stimulated cAMP accumulation by intact cells ( ) inhibition of basal release of IR-aMSH by intact cells ( J occupancy of specific [3H]-spiroperidol binding sites in a cell-free homogenate (Q) and inhibition of isoproterenol-stimulated adenylate cyclase activity in a cell-free homogenate (M), the effect achieved with the indicated concentration of apomorphine is expressed as a percentage of the maximal effect of apomorphine (33). 

Figure 2. Effect of the guanine nucleotide Gpp(NH)p on competition of the agonist n-propylapomorphine for [3H]spiroperidol binding.

Figure 1. Apomorphine competition curves of [3H]spiroperidol binding, in the absence and presence of 50 /xM GppNHp. Membranes were preincubated for 10 min at 37 °C and then incubated for 15 min at 37 °C with 100 pM [3H]spiroperidol. Specific binding was defined in the presence of 10 /xM (-)-sulpiride, and accounted for 70-75% of total binding.

Figure 3. Apomorphine competition curve of [3H]spiroperidol binding. Membranes were preincubated for 30 min at 37 °C, then incubated for 45 min at 37 °C with 100 pM [3H]spiroperidol.

A very intriguing observation noted above was the possibility of presynaptic dopamine agonist activity with SK F 87516 and SK F 85174. The inhibitions of the constrictor response and the 3H -norepinephrine release induced by brief intermittent periarterial sympathetic nerve stimulation of the perfused rabbit ear artery is a convenient in vitro assay for presynaptic dopamine agonist activity (30). In this preparation, both SK F 85174 and SK F 87516 inhibited both stimulation responses with an EC50 of about 100 riM. Another measure of D-2 activity is inhibition of specific spiroperidol binding (20). Comparison of these data (Table I) showed that SK F 85174 is thirty times as potent as dopamine, and thus is a potent D-2 agonist. However, the activity in adenylate cyclase stimulation indicates that this compound may be best described as a D-l/D-2 agonist (19, 20). 

As indicated in Table I, I-III and their R and S optical antipodes were studied for dopaminergic activity in four primary tests (1) stimulation of central DA-sensitive adenylate cyclase (2, 35), (2) displacement of [%]-spiroperidol binding to rat caudate homogenate (35, 40), (3) induction of rotations in rats with unilateral lesions of the left substantia nigra (2, ... 

COMPOUND r4 AVOIDANCE ABD50 mg/kg po 3H-SPIROPERIDOL BINDING IC50 nM... 

Creese I, Snyder SH (1979) Nigrostriatal lesions enhance striatal 3H-apomorphine and 3H-spiroperidol binding. Eur J Pharmacol 56 277—281. 

Heikkila RE, Shapiro BS, Duvoisin RC (1981) The relationship between loss of dopamine nerve terminals, striatal [3H]spiroperidol binding and rotational behavior in unilaterally 6-hydroxydopamine-lesioned rats. Brain Res 211 285—292. 

Binding data supplied by Seeman and his colleagues have indicated that in the striatum low concentrations of APO bind primarily to pre-synaptic receptors while low concentrations of neuroleptics (e.g., haloperidol) bind preferentially to postsynaptic receptors.Thus injection of 6-OH-DA into the substantia nigra, which destroys presynaptic nerve terminals but spares postsynaptic neurons, decreases the binding of H-APO and increases the binding of H-haloperidol.However, it must be noted here that Creese and Snyder have reported that a similar lesion produces increases in both H-APO and H-spiroperidol binding.The technical differences underlying this discrepancy are not yet known. The increased... 

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