Behavioural studies on dopamine receptors in the central nervous system of the rat

Mustafa, Ali Ahmed (1982) Behavioural studies on dopamine receptors in the central nervous system of the rat. University of Southampton, Doctoral Thesis.

Abstract

A study has been made of the effect of some ergot alkaloids and their derivatives on angiotensin-Il-induced drinking in rats. Ergometrine was the most potent in blocking angiotensin-induced thirst. Lysergic acid diethylamide (LSD) and methysergide showed some moderate activity but bromolysergic acid diethylamide (BOL-148) was inactive. In contrast, carbachol-induced drinking was unaffected by ergometrine suggesting that angiotensin-induced drinking occurs via a mechanism different from that of carbachol. Unilateral intra-nigral injections of ergometrine in rats caused intense-and dose-dependent contraversive circling behaviour. This behaviour was blocked by previous injections (i.p.) of fluphenazine but not by prior intra-nigral injections of fluphenazine, (±)-sulpiride, 5hydroxytryptamine or cyprohepLadine. 6-Hydroxydopamine lesions of the ipsilateral nigrostriatal tract were similarly ineffective. The involvement of a non-dopaminergic mechanism in this behaviour is discussed. Ergometrine induced strong and long-lasting stimulation of locomotor activity following bilateral injection into the nucleus accumbens of rats. Other ergot derivatives such as bromocriptine, pergolide or lisuride were similarly active. The ergometrine response was specifically blocked by neuroleptic drugs, but was unaffected by a-methyl-p-tyrosine (i.p.) or cyproheptadine (intra-accumbens) pretreatments. The dopamine analogue, ADTN (2-amino-6,7-dihydroxy-l,2,3,4tetrahydronaphthalene) induced strong and long-lasting stimulation of locomotor activity following bilateral injection into the nucleus accumbens of conscious rats; an efffect which was blocked by low doses of (±)sulpiride. Similarly, the 2-aminotetralin, T-15520 (trans-2-amino-l,5,6trihydroxy-1,2,3,4-tetrahydronaphthalene) caused intense locomotor stimulation while its cis-isomer was inactive. This effect of the 2-aminotetralin was blocked by fluphenazine but not by the S-adrenoceptor antagonist, dl-propranolol, suggesting an interaction with specific dopamine receptors.-N-(2-chloroethyl) norapomorphine (-NCA) is a drug which causes longlasting blockade of dopamine receptors, possibly by alkylating the receptor. -NCA blocked part of the hypermotility induced by ADTN or pergolide following bilateral injection into the nucleus accumbens. The initial activity induced by either drug was not blocked by -NCA. It did, however, block the entire locomotor activity produced by the dopamine agonist, SK8F 38393. Surprisingly, -NCA did not block the hypermotility caused following the intra-accumbens injection of ergometrine.

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