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  • 1
    ISSN: 1432-2072
    Keywords: Clozapine ; Sulpiride ; Haloperidol ; Dopamine receptors ; Sterotypy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats received therapeutically equivalent doses of either haloperidol (1.7–1.9 mg/kg/day), sulpiride (112–116 mg/kg/day) or clozapine (30–35 mg/kg/day) continuously for 4 weeks. Treatment with haloperidol, but not sulpiride or clozapine, caused inhibition of stereotyped behaviour induced by apomorphine (0.125–0.25 mg/kg SC). Following drug withdrawal for up to 7 days, haloperidol and sulpiride, but not clozapine treatment caused an exaggeration of stereotyped behaviour induced by apomorphine. Bmax values for striatal 3H-spiperione binding were erevated in animals treated for 2 and 4 weeks with haloperidol, but not with sulpiride or clozapine. Following drug withdrawal, haloperidol, but not sulpiride or clozapine, treatment caused an increase in Bmax for striatal 3H-piperone binding. Bmax values for striatal 3H-NPA binding revealed no change during haloperidol or clozapine treatment. Sulpiride treatment for 1 week caused an increase in Bmax for 3H-NPA binding, which returned to control levels at 2 and 4 weeks. Following drug withdrawal, there was an increase in Bmax for 3H-NPA binding in rats treated with haloperidol and sulpiride, but not clozapine. On continuous treatment and following withdrawal from haloperidol, sulpiride, or clozapine the ability of dopamine to stimulate striatal adenylate cyclase activity did not differ from that in control animals. Repeated administration of sulpiride or clozapine may not induce striatal dopamine receptor supersensitivity when given in clinically relevant doses, although haloperidol does.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 55 (1984), S. 243-252 
    ISSN: 1432-1106
    Keywords: Circling behaviour ; Substantia nigra ; Dopamine receptors ; Dopamine ; Apomorphine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Unilateral intranigral injections of dopamine in conscious rats pretreated with nialamide resulted in either ipsiversive or contraversive rotation depending upon the site of injection. Injection of dopamine (50 μg) into the zona compacta of the substantia nigra induced weak ipsiversive or mixed ipsiversive and contraversive rotation. Injection of dopamine (12.5–50.0 μg) into zona reticulata of substantia nigra induced only contraversive circling. Destruction of the ipsilateral medial forebrain bundle (MFB) using 6-hydroxydopamine (6-OHDA) abolished ipsiversive circling but enhanced contraversive circling produced by dopamine or apomorphine. The combination of a unilateral 6-OHDA lesion of MFB with a kainic acid or electrolesion of the ipsilateral strio-nigral and pallido-nigral pathways reduced contraversive circling to intranigral apomorphine (10 μg). Ipsiversive circling produced following intranigral injection of dopamine is dependent upon the integrity of ascending dopamine neurones. Contraversive rotation is independent of ascending dopamine pathways but is reliant upon afferent input to the substantia nigra from the striatum and/or globus pallidus.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2072
    Keywords: Chronic neuroleptic ; Dopamine ; Supersensitivity ; Striatum ; Mesolimbic area
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous work has shown that 6–12 months continuous trifluoperazine (TFP) administration to rats causes striatal dopamine receptor supersensitivity. We have now replicated our original findings in the striatum and report concurrent changes in mesolimbic dopamine function during chronic TFP (2.8–4.0 mg/kg/day) administration for 6 months. Initial inhibition of apomorphine-induced stereotyped behaviour, which lasted for 2 weeks after the beginning of drug administration, was replaced by an exaggerated response to apomorphine (0.5 mg/kg SC) after 6 months drug intake. Striatal dopamine sensitive adenylate cyclase activity was inhibited at 1 and 3 months, but by 6 months was enhanced compared to control values. Mesolimbic adenylate cyclase activity was inhibited after 2 weeks and thereafter returned to control levels. Dopamine-identified 3H-spiperone binding sites (Bmax) in the striatum were increased by 2 weeks, reduced at 1 month and increased again at 6 months. In mesolimbic areas Bmax was increased at 2 weeks and 1 month but thereafter returned to control levels. The dissociation constant (k D) of specific 3H-spiperone binding was increased in the striatum and mesolimbic areas at 1 month and 2 weeks respectively. The results show differential changes in dopamine function in striatal and mesolimbic brain areas during 6 months continuous TFP administration to rats.
    Type of Medium: Electronic Resource
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