Involvement of D1 dopamine receptors in the nicotine-induced neuro-endocrine effects and depletion of diencephalic catecholamine stores in the male rat.
Male rats were treated acutely with nicotine (4 x 2 mg/kg, 30-min time intervals, total treatment time 2 h) or exposed to cigarette smoke from 4 x 1 cigarette (30-min time intervals, total treatment time 2 h). Some rats were pretreated with the D1 dopamine (DA) receptor antagonist SCH 23390 (0.1-3.0 mg/kg, i.p.), or with the D2 DA receptor antagonists remoxipride and raclopride (1 mg/kg, i.p.), or with the 5-hydroxytryptamine 2 (5-HT2) receptor antagonist ketanserin (0.3 mg/kg, i.p.) 5 min before nicotine treatment or the acute intermittent exposure to cigarette smoke. Some rats were treated with the D1 DA receptor agonist SK&F 38393 (1-10 mg/kg, i.p.) 15 min, 30 min or 2 h before decapitation. Hypothalamic and pre-optic catecholamine (CA) levels were measured by quantitative histofluorimetry in discrete DA and noradrenaline (NA) nerve terminal systems. Serum thyroid-stimulating hormone (TSH), prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), vasopressin, corticosterone and testosterone levels were determined by radioimmunoassay procedures. Nicotine treatment and to a minor degree also acute intermittent exposure to cigarette smoke produced a reduction in serum prolactin, LH and TSH but not in serum FSH, vasopressin and testosterone levels. Nicotine treatment also increased serum corticosterone levels. Pretreatment with the D1 DA receptor antagonist SCH 23390 (1-3 mg/kg) counteracted the lowering of serum LH, but not of prolactin and TSH levels induced by nicotine or exposure to cigarette smoke. SCH 23390 alone (1-3 mg/kg) increased serum TSH levels. Remoxipride, raclopride or ketanserin did not counteract any of the neuro-endocrine actions induced by nicotine treatment. However, ketanserin alone lowered serum prolactin levels. SK&F 38393 increased serum TSH, prolactin and LH levels. It was found that nicotine treatment and exposure to cigarette smoke with few exceptions produced a depletion of CA stores in NA and DA nerve terminals of the hypothalamus, pre-optic area and median eminence which was counteracted by SCH 23390 (1 mg/kg) but not by remoxipride, raclopride (1 mg/kg) or ketanserin (0.3 mg/kg). The results indicate that D1 but not D2 DA or 5-HT2 receptors may modulate the NA and DA release in the median eminence, the hypothalamus and the pre-optic area induced by nicotinic cholinoceptor activation. Furthermore, D1 DA receptors in the median eminence may at least in part mediate the inhibitory effects of nicotine on LH but not on TSH and prolactin secretion, although there appears to exist a D1 DA receptor in the median eminence which inhibits TSH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
Andersson
K
K
Department of Histology and Neurobiology, Karolinska Institutet, Stockholm, Sweden.
Fuxe
K
K
Eneroth
P
P
Härfstrand
A
A
Agnati
L F
LF
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D004027:Diencephalon / Q000187:drug effects / Q000502:physiology*; D018492:Dopamine Antagonists; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D010908:Pituitary Hormones, Anterior / Q000097:blood / Q000378:metabolism*; D020891:Raclopride; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012016:Reference Values; D017330:Remoxipride; D012457:Salicylamides / Q000494:pharmacology; D012906:Smoke; D013739:Testosterone / Q000097:blood / Q000378:metabolism
D001549:Benzamides; D001552:Benzazepines; D018492:Dopamine Antagonists; D010908:Pituitary Hormones, Anterior; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D012906:Smoke; D017330:Remoxipride; D013739:Testosterone; D020891:Raclopride; D009538:Nicotine; D007650:Ketanserin; D003345:Corticosterone