Dopamine Agonist-induced Stereotypic Grooming and Self-mutilation Following Striatal Dopamine Depletion

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 1986 Jan 1

PMID 3097724

Citations 5

Authors

S L Hartgraves

P K Randall

Affiliations

Soon will be listed here.

Abstract

Rats with bilateral 6-OHDA-induced striatal lesions exhibit altered apomorphine-induced behavior compared to the typical response seen in intact rats. This response is characterized by stereotypic grooming behavior which is transformed to compulsive and intense biting at higher doses. Other agonists, pergolide, bromocriptine, N-n-propylnorapomorphine and L-dopa/carbidopa, caused the same response. Direct intrastriatal infusion of apomorphine after 6-OHDA-induced lesions of the striata also produced this response, while similar SKF 38393 infusion caused more licking than biting, directed at the abdomen instead of the forepaws. The dopamine receptor antagonists haloperidol, SCH 23390 and sulpiride effectively blocked apomorphine-induced behaviors in dopamine-depleted animals. This altered behavior was not observed in rats with dopamine depletion in nucleus accumbens (NAS), nor did additional NAS lesions in rats with existing striatal lesions affect the behavior. Further, high doses of apomorphine (up to 60 mg/kg) failed to induce stereotypic grooming in unlesioned rats. We therefore propose that altered apomorphine-induced behavior is a unique consequence of striatal dopamine depletion and not just an intense form of normal stereotypic activity.

Citing Articles

Molecular Pathways, Neural Circuits and Emerging Therapies for Self-Injurious Behaviour.

Zhang K, Ibrahim G, Venetucci Gouveia F Int J Mol Sci. 2025; 26(5).

PMID: 40076564 PMC: 11900092. DOI: 10.3390/ijms26051938.

Striatal Interneuron Imbalance in a Valproic Acid-Induced Model of Autism in Rodents Is Accompanied by Atypical Somatosensory Processing.

Ibanez-Sandoval D, Hidalgo-Balbuena A, Velazquez Contreras R, Saderi N, Flores G, Rueda-Orozco P eNeuro. 2024; 11(12).

PMID: 39572246 PMC: 11653103. DOI: 10.1523/ENEURO.0326-24.2024.

Dysregulation of Corticostriatal Connectivity in Huntington's Disease: A Role for Dopamine Modulation.

Rangel-Barajas C, Rebec G J Huntingtons Dis. 2016; 5(4):303-331.

PMID: 27983564 PMC: 5181679. DOI: 10.3233/JHD-160221.

Mother/offspring co-administration of the traditional herbal remedy yokukansan during the nursing period influences grooming and cerebellar serotonin levels in a rat model of neurodevelopmental disorders.

Muneoka K, Kuwagata M, Ogawa T, Shioda S Cerebellum. 2014; 14(2):86-96.

PMID: 25315739 DOI: 10.1007/s12311-014-0611-2.

The antinociceptive and anti-inflammatory activities of Aspidosperma tomentosum (Apocynaceae).

Aquino A, Cavalcante-Silva L, da Matta C, Epifanio W, Aquino P, Santana A ScientificWorldJournal. 2013; 2013:218627.

PMID: 23781151 PMC: 3679822. DOI: 10.1155/2013/218627.

References

Yurek D, Randall P . Simultaneous catalepsy and apomorphine-induced stereotypic behavior in mice. Life Sci. 1985; 37(18):1665-73. DOI: 10.1016/0024-3205(85)90293-0. View

Breese G, BAUMEISTER A, McCown T, Emerick S, Frye G, Crotty K . Behavioral differences between neonatal and adult 6-hydroxydopamine-treated rats to dopamine agonists: relevance to neurological symptoms in clinical syndromes with reduced brain dopamine. J Pharmacol Exp Ther. 1984; 231(2):343-54. PMC: 3060042. View

Jackson E, Neumeyer J, Kelly P . Behavioral activity of some novel aporphines in rats with 6-hydroxydopamine lesions of caudate or nucleus accumbens. Eur J Pharmacol. 1983; 87(1):15-23. DOI: 10.1016/0014-2999(83)90045-6. View

Molloy A, Waddington J . Dopaminergic behaviour stereospecific promoted by the D1 agonist R-SK & F 38393 and selectively blocked by the D1 antagonist SCH 23390. Psychopharmacology (Berl). 1984; 82(4):409-10. DOI: 10.1007/BF00427697. View

Erinoff L, Kelly P, Basura M, Snodgrass S . Six-hydroxydopamine induced hyperactivity: neither sex differences nor caffeine stimulation are found. Pharmacol Biochem Behav. 1984; 20(5):707-13. DOI: 10.1016/0091-3057(84)90189-8. View

Creese I, Iversen S . Blockage of amphetamine induced motor stimulation and stereotypy in the adult rat following neonatal treatment with 6-hydroxydopamine. Brain Res. 1973; 55(2):369-82. DOI: 10.1016/0006-8993(73)90302-8. View

Delean A, Munson P, Rodbard D . Simultaneous analysis of families of sigmoidal curves: application to bioassay, radioligand assay, and physiological dose-response curves. Am J Physiol. 1978; 235(2):E97-102. DOI: 10.1152/ajpendo.1978.235.2.E97. View

Marshall J, Ungerstedt U . Supersensitivity to apomorphine following destruction of the ascending dopamine neurons: quantification using the rotational model. Eur J Pharmacol. 1977; 41(4):361-7. DOI: 10.1016/0014-2999(77)90256-4. View

Rebec G, Bashore T . Critical issues in assessing the behavioral effects of amphetamine. Neurosci Biobehav Rev. 1984; 8(1):153-9. DOI: 10.1016/0149-7634(84)90030-7. View

10.

LJUNGBERG T, Ungerstedt U . Reinstatement of eating by dopamine agonists in aphagic dopamine denervated rats. Physiol Behav. 1976; 16(3):277-83. DOI: 10.1016/0031-9384(76)90133-5. View

11.

Ungerstedt U . Adipsia and aphagia after 6-hydroxydopamine induced degeneration of the nigro-striatal dopamine system. Acta Physiol Scand Suppl. 1971; 367:95-122. DOI: 10.1111/j.1365-201x.1971.tb11001.x. View

12.

Mandel R, Randall P . Quantification of lesion-induced dopaminergic supersensitivity using the rotational model in the mouse. Brain Res. 1985; 330(2):358-63. DOI: 10.1016/0006-8993(85)90698-5. View

13.

Moore K, Phillipson O . Effects of dexamethasone on phenylethanolamine N-methyltransferase and adrenaline in the brains and superior cervical ganglia of adult and neonatal rats. J Neurochem. 1975; 25(3):289-94. DOI: 10.1111/j.1471-4159.1975.tb06968.x. View

14.

Umezu K, Moore K . Effects of drugs on regional brain concentrations of dopamine and dihydroxyphenylacetic acid. J Pharmacol Exp Ther. 1979; 208(1):49-56. View

15.

Schoenfeld R, Uretsky N . Altered response to apomorphine in 6-hydroxydopamine-treated rats. Eur J Pharmacol. 1972; 19(1):115-8. DOI: 10.1016/0014-2999(72)90085-4. View

16.

Hartgraves S, Kelly P . Inhibition of drug-induced circling by GABA-ergic activity in the nucleus accumbens. Brain Res Bull. 1983; 11(3):315-20. DOI: 10.1016/0361-9230(83)90167-3. View

17.

Osterburg H, Donahue H, Severson J, Finch C . Catecholamine levels and turnover during aging in brain regions of male C57BL/6J mice. Brain Res. 1981; 224(2):337-52. DOI: 10.1016/0006-8993(81)90864-7. View

18.

Burt D, Creese I, Snyder S . Antischizophrenic drugs: chronic treatment elevates dopamine receptor binding in brain. Science. 1977; 196(4287):326-8. DOI: 10.1126/science.847477. View

19.

Lesch M, Nyhan W . A FAMILIAL DISORDER OF URIC ACID METABOLISM AND CENTRAL NERVOUS SYSTEM FUNCTION. Am J Med. 1964; 36:561-70. DOI: 10.1016/0002-9343(64)90104-4. View

20.

Lloyd K, Hornykiewicz O, Davidson L, Shannak K, Farley I, Goldstein M . Biochemical evidence of dysfunction of brain neurotransmitters in the Lesch-Nyhan syndrome. N Engl J Med. 1981; 305(19):1106-11. DOI: 10.1056/NEJM198111053051902. View