Hypothalamus – Response to early paracetamol exposure in male rats offspring

• Published in: International journal of developmental neuroscience Vol. 76; no. 1; pp. 1 - 5
• Main Authors: Blecharz-Klin, Kamilla, Wawer, Adriana, Pyrzanowska, Justyna, Piechal, Agnieszka, Jawna-Zboińska, Katarzyna, Widy-Tyszkiewicz, Ewa
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.08.2019; Elsevier BV
• Subjects: 3,4-Dihydroxyphenylacetic Acid - metabolism; Acetaminophen; Acetaminophen - toxicity; Acetic acid; Amino acids; Amino Acids - metabolism; Analgesics; Analgesics, Non-Narcotic - toxicity; Animals; Animals, Newborn; Biochemical analysis; Body temperature; Brain Chemistry - drug effects; Dopamine; Dopamine - metabolism; Dopamine receptors; Exposure; Female; Fever; Glutamates - metabolism; Glutamic acid; Homovanillic acid; Homovanillic Acid - metabolism; Hypothalamus; Hypothalamus - drug effects; Hypothalamus - growth & development; Hypothalamus - metabolism; Male; Metabolites; Methoxyhydroxyphenylglycol - metabolism; Monoamines; Neurotransmission; Noradrenaline; Norepinephrine; Norepinephrine - metabolism; Offspring; Paracetamol; Pituitary; Pregnancy; Rats; Rats, Wistar; Rodents; Synaptic Transmission - drug effects; Paracetamol; Hypothalamus; Acetaminophen; Neurotransmission
• ISSN: 0736-5748; 1873-474X
• DOI: 10.1016/j.ijdevneu.2019.05.004

[Display omitted] •Early paracetamol treatment changes hypothalamic neurotransmission in rats’ offspring.•Drug has a significant effect on dopaminergic and noradrenergic neurotransmission.•Paracetamol affects concentration of glutamic acid in hypothalamus. One of the reasons for using paracetamol during pregnancy is fever. The brain structure responsible for maintaining proper body temperature, but also for controlling some endocrine aspects is hypothalamus. In this study we examined the effect of early pretreatment of paracetamol on hypothalamic neurotransmission in rats’ offspring. We used two-month old rats previously exposed to paracetamol at doses of 5 (P5) and 15 mg/kg (P15) during gestational development and next postnatally. The concentration of monoamines, their metabolites and amino acids in hypothalamus was chromatographically determined. The results of biochemical analysis were compared with the Control animals (Con). We found differences between groups in the concentration of main noradrenaline metabolite in hypothalamus. The control group had significantly higher level of 3-methoxy-4-hydroxyphenylglycol (MHPG) compared with rats exposed to paracetamol (F(2,27) = 7.96, p < 0.005). Simultaneously the level of dopamine (DA) (F(2,27) = 4.33, p < 0.05) and its metabolite - homovanillic acid (HVA) (F(2,27) = 17.03, p < 0.005) was increased in the hypothalamus of animals treated with lower dose of the drug. Biochemical analyses show an increase in 3,4-dihydroxyphenyl acetic acid (DOPAC) concentration in P5 group compared to the control rats and group treated with higher dose of paracetamol (F(2,27) = 7.37, p < 0.005). In the hypothalamus significant decrease of glutamic acid concentration was also observed in the group treated with paracetamol at dose of 5 mg. These results demonstrated that paracetamol had a significant effect on dopaminergic and noradrenergic neurotransmission and changed the concentration of glutamic acid in hypothalamus - heat-regulating center and important element of hypothalamic-pituitary- gonadal axis.