The anti-dopaminergic agent, haloperidol, antagonises the feminising effect of neonatal serotonin on sexually dimorphic hypothalamic nuclei and tyrosine hydroxylase immunoreactive neurones.
There is a transient fall in hypothalamic serotonin (5-hydroxytryptamine; 5-HT) activity in the second week post partum in male but not female rats. When this fall is masked by administration of the 5-HT(2) agonist (-) 2,5-dimethoxy-4-iodophenyl]-2-aminopropane hydrochloride [(-)DOI], over days 8-16 post partum, males are feminised in adulthood. To investigate whether the effect of 5-HT is mediated by dopamine and whether testosterone exerts its masculinising effect by reducing 5-HT and dopamine activity, male pups were treated with (-)DOI alone or together with the dopamine antagonist, haloperidol, over days 8-16 post partum, whereas females were treated with testosterone propionate on day 2 post partum. In adulthood, the volumes of the anteroventral periventricular nucleus (AVPV), sexually dimorphic nucleus of the preoptic area (SDN-POA) and arcuate nucleus (ARC) were determined, together with the number of tyrosine hydroxylase-immunoreactive (TH-ir) cells and fibres within them. The concentrations of 5-HT, dopamine and their metabolites were also measured. (-)DOI treatment increased the volume of the AVPV, decreased that of the SDN-POA and increased the number of TH-ir cells in the AVPV. These feminising effects were antagonised by concurrent haloperidol treatment. Neonatal testosterone propionate masculinised the volumes of the female AVPV and SDN-POA and reduced the number of TH-ir cells in the AVPV. Dopamine and 5-HT turnover in the AVPV was greater in female compared to male rats and neonatal testosterone propionate reduced dopamine concentration in the female AVPV. Neonatal (-)DOI had no effect on dopamine and 5-HT activity in the AVPV but increased both in the ARC. The findings that TH-ir neurone number and dopamine activity are greater in the female AVPV; the feminising effect of 5-HT is prevented by a haloperidol; and the masculinising effect of testosterone propionate is accompanied by a decrease in TH-ir neurone number and dopamine concentration in the female AVPV, suggest that dopamine is involved in hypothalamic sexual differentiation and may mediate the effect of 5-HT.
Wilson
C A
CA
Division of Basic Medical Sciences St George's, University of London, London, UK.
Dakin
C L
CL
Rico
J A
JA
Golmohamad
A
A
Ahmad-Jauhari
Y
Y
Davies
D C
DC
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002491:Central Nervous System Agents / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology*; D005260:Female; D006220:Haloperidol / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects* / Q000254:growth & development*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D049590:Postpartum Period; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D012727:Sex Characteristics; D043343:Testosterone Propionate / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000662:Amphetamines; D002491:Central Nervous System Agents; D018492:Dopamine Antagonists; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D014446:Tyrosine 3-Monooxygenase; D006220:Haloperidol; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D004298:Dopamine; D043343:Testosterone Propionate