Effects of Combined Pre‐ and Postnatal Treatment with Nicotine on Hypothalamic Catecholamine Nerve Terminal Systems and Neuroendocrine Function in the 4‐Week Old and Adult Male and Female Diestrous Rat
Authors: Jansson A. , Andersson K. , Fuxe K. , Bjelke B. , Eneroth P. 
Published: September 2006

Male and female Sprague‐Dawley rats were treated with nicotine during the prenatal period and the first three postnatal weeks (the pregnant and lactating rats were given nicotine hydrogen (+) tartrate (165 mg/l) in the tap water). Catecholamine fluorescence was evaluated using quantitative histofluorometry on brain sections treated according to Falck‐Hillarp methodology. In order to evaluate catecholamine utilization in discrete hypothalamic catecholamine nerve terminal networks, the αMT‐ (α‐methyl‐(±)‐p‐tyrosine methyl ester) induced catecholamine disappearance was studied 2 h following the tyrosine hydroxylase inhibition. The body weight was reduced in both the male and female rats from 3 weeks of age until 9 weeks of age following pre‐ and postnatal treatment with nicotine.

Following one week of withdrawal from pre‐ and postnatal treatment with nicotine, an increased catecholamine utilization was observed in the medial and lateral palisade zones of the median eminence mainly in the female rat. In the female rat, reduced prolactin serum levels were found both in the presence and absence of αMT treatment as well as reduced luteinizing hormone concentration in the presence of αMT treatment.

At 6 months of age indications of a maintained, weak activation of the catecholamine nerve terminal systems in the medial palisade zones of the median eminence were observed in male rats pre‐ and postnatally treated with nicotine. Furthermore, increased noradrenaline levels were found in the paraventricular hypothalamic nucleus. An increase in serum luteinizing hormone levels was also found in these rats. In the 7‐month old diestrous rat, maintained marked increases in catecholamine utilization in the medial and lateral palisade zones of the median eminence were found following treatment with nicotine during the pre‐ and postnatal period. A significant reduction of nigral dopamine stores was also demonstrated. The serum levels of thyroid stimulating hormone, prolactin and luteinizing hormone were unchanged in these rats both in the presence and absence of tyrosine hydroxylase inhibition. Finally, pre‐ and postnatal treatment with nicotine did not alter [3H]nicotine binding (quantitative receptor autoradiography) in cortical, striatal and thalamic areas of the adult diestrous rat.

The results demonstrate that pre‐ and postnatal treatment with nicotine in the drinking water produces permanent activations of the catecholamine nerve terminal networks of the external layer of the median eminence mainly in the female rat. These changes appear to be associated with reduced serum prolactin levels in the 4‐week old female rat. Sex‐specific changes occur in discrete noradrenaline nerve terminal systems. The observed changes may have functional consequences for neuroendocrine regulation and for the regulation of food and water intake as well as sex‐specific responses to stress in the male versus the female rat. Nicotine‐induced disturbances in brain cell replication and differentiation may underlie the permanent alteration found in discrete catecholamine neuron systems after pre‐ and postnatal exposure to this drug.