PubMed · 559237
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W E Campbell. 1977. Pot pourri.. https://pubmed.ncbi.nlm.nih.gov/559237/
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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.
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Behavioral toxicology is an emerging field which is becoming increasingly important in risk assessment of exposure to neurotoxic substances, due to the high sensitivity of behavior towards neurotoxic action and the integration in behavioral functions of several underlying processes and neurofunctions, such as motor, sensory, attention, motivational. Whenever it is difficult to isolate the relative contribution of sensory, motor, arousal, or cognitive factors that contribute to an observed behavioral change, possible mechanism of behavioral alteration may rely on the involvement of neurotransmitters, such as the dopaminergic system and catecholamines metabolism. Examples are given of different behavioral types of changes induced in humans by organic solvents (styrene), metals (manganese) and anaesthetic gases, based on a possible common underlying mechanism of toxicity.