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Inhibition of amphetamine- and apomorphine-induced behavioural effects by neuropeptide Y Y(1) receptor antagonist BIBO 3304.
Neuropharmacology 2000; 39(7):1292-302N

Abstract

Neuropeptide Y (NPY) has an important role in the regulation of stress responses and feeding behaviour. There is evidence that some effects elicited by NPY occur due to modulation of action of regular neurotransmitters. The main objective of the present study was to test behavioural effects of the novel neuropeptide Y (NPY) Y(1) receptor antagonist (R)-N-[[4-(aminocarbonylaminomethyl)-phenyl]methyl]-N(2)-(diphe nylacetyl)-argininamide trifluoroacetate (BIBO 3304) on dopamine-dependent behaviour. Intracerebroventricular administration of BIBO 3304 (1, 10, 50 nmol) had no effect on locomotor activity as measured by number of rearings and number of squares visited in an open field test in rats, but at 50 nmol dose defecation was significantly increased. BIBO 3304 (10 nmol) reduced amphetamine-induced increases in horizontal and vertical activity whereas its S-configurated enantiomer BIBO 3457 was inactive. In an open field test BIBO 3304 (10 nmol) inhibited purposeless running in rats sensitized to direct dopaminergic agonist apomorphine (0.5 mg/kg, s.c.). BIBO 3304 (10 nmol but not 1 nmol, i.c.v.) reduced fighting in apomorphine-induced aggression paradigm. Apomorphine-induced aggression was reduced by another, structurally similar, but less potent NPY Y(1) receptor antagonist BIBP 3226 (10 nmol, i.c.v.). A lower dose of BIBP 3226 (1 nmol, i.c.v.) was inactive. Concomitant administration of BIBO 3304 (10 nmol) with low doses of apomorphine (0.5 mg/kg s.c.) over the course of 10 days failed to prevent the development of apomorphine-induced aggressiveness. These data demonstrate that behavioural response to indirectly (amphetamine) and directly (apomorphine) acting dopaminergic stimulants is inhibited by NPY Y(1) receptor antagonists and suggest that NPY Y(1) receptor activation might be important in pathophysiology of disorders associated with hyperactivity of dopaminergic pathways, such as psychosis, schizophrenia and drug abuse. We propose that the effects of BIBO 3304 on amphetamine/apomorphine-induced locomotion and apomorphine-induced aggressiveness are due to modulation of postsynaptic dopaminergic responses rather than direct effects of NPY Y(1) receptor antagonists on dopamine or NPY release.

Authors+Show Affiliations

Department of Pharmacology, Faculty of Medicine, University of Tartu, Ravila 19, 50411, Tartu, Estonia. ants.kask@ut.eeNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10760371

Citation

Kask, A, and J Harro. "Inhibition of Amphetamine- and Apomorphine-induced Behavioural Effects By Neuropeptide Y Y(1) Receptor Antagonist BIBO 3304." Neuropharmacology, vol. 39, no. 7, 2000, pp. 1292-302.
Kask A, Harro J. Inhibition of amphetamine- and apomorphine-induced behavioural effects by neuropeptide Y Y(1) receptor antagonist BIBO 3304. Neuropharmacology. 2000;39(7):1292-302.
Kask, A., & Harro, J. (2000). Inhibition of amphetamine- and apomorphine-induced behavioural effects by neuropeptide Y Y(1) receptor antagonist BIBO 3304. Neuropharmacology, 39(7), pp. 1292-302.
Kask A, Harro J. Inhibition of Amphetamine- and Apomorphine-induced Behavioural Effects By Neuropeptide Y Y(1) Receptor Antagonist BIBO 3304. Neuropharmacology. 2000 Apr 27;39(7):1292-302. PubMed PMID: 10760371.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of amphetamine- and apomorphine-induced behavioural effects by neuropeptide Y Y(1) receptor antagonist BIBO 3304. AU - Kask,A, AU - Harro,J, PY - 2000/4/13/pubmed PY - 2000/8/19/medline PY - 2000/4/13/entrez SP - 1292 EP - 302 JF - Neuropharmacology JO - Neuropharmacology VL - 39 IS - 7 N2 - Neuropeptide Y (NPY) has an important role in the regulation of stress responses and feeding behaviour. There is evidence that some effects elicited by NPY occur due to modulation of action of regular neurotransmitters. The main objective of the present study was to test behavioural effects of the novel neuropeptide Y (NPY) Y(1) receptor antagonist (R)-N-[[4-(aminocarbonylaminomethyl)-phenyl]methyl]-N(2)-(diphe nylacetyl)-argininamide trifluoroacetate (BIBO 3304) on dopamine-dependent behaviour. Intracerebroventricular administration of BIBO 3304 (1, 10, 50 nmol) had no effect on locomotor activity as measured by number of rearings and number of squares visited in an open field test in rats, but at 50 nmol dose defecation was significantly increased. BIBO 3304 (10 nmol) reduced amphetamine-induced increases in horizontal and vertical activity whereas its S-configurated enantiomer BIBO 3457 was inactive. In an open field test BIBO 3304 (10 nmol) inhibited purposeless running in rats sensitized to direct dopaminergic agonist apomorphine (0.5 mg/kg, s.c.). BIBO 3304 (10 nmol but not 1 nmol, i.c.v.) reduced fighting in apomorphine-induced aggression paradigm. Apomorphine-induced aggression was reduced by another, structurally similar, but less potent NPY Y(1) receptor antagonist BIBP 3226 (10 nmol, i.c.v.). A lower dose of BIBP 3226 (1 nmol, i.c.v.) was inactive. Concomitant administration of BIBO 3304 (10 nmol) with low doses of apomorphine (0.5 mg/kg s.c.) over the course of 10 days failed to prevent the development of apomorphine-induced aggressiveness. These data demonstrate that behavioural response to indirectly (amphetamine) and directly (apomorphine) acting dopaminergic stimulants is inhibited by NPY Y(1) receptor antagonists and suggest that NPY Y(1) receptor activation might be important in pathophysiology of disorders associated with hyperactivity of dopaminergic pathways, such as psychosis, schizophrenia and drug abuse. We propose that the effects of BIBO 3304 on amphetamine/apomorphine-induced locomotion and apomorphine-induced aggressiveness are due to modulation of postsynaptic dopaminergic responses rather than direct effects of NPY Y(1) receptor antagonists on dopamine or NPY release. SN - 0028-3908 UR - https://www.unboundmedicine.com/medline/citation/10760371/Inhibition_of_amphetamine__and_apomorphine_induced_behavioural_effects_by_neuropeptide_Y_Y_1__receptor_antagonist_BIBO_3304_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028390899001999 DB - PRIME DP - Unbound Medicine ER -