Centrally administered choline increases plasma prolactin levels in conscious rats M. Sibel Gu ¨ru ¨n*, Vahide Savci, Ismail H. Ulus, Burhan K. Kiran Department of Pharmacology, Uludag University Medical Faculty, Bursa, TR-16059, Turkey Received 20 June 1997; received in revised form 25 July 1997; accepted 25 July 1997 Abstract Intracerebroventricular (i.c.v.) administration of choline, a precursor of acetylcholine (ACh) increased plasma prolactin levels in a time and dose-dependent manner in conscious rats. Pretreatment of rats with the cholinergic muscarinic antagonist, atropine (10 mg, i.c.v.), blocked the increase in plasma prolactin level. The increase was not influenced by pretreatment with the cholinergic nicotinic antagonist, mecamylamine (50 mg, i.c.v.). Pretreatment with hemicholinium-3 (HC-3; 20 mg, i.c.v.), a high affinity choline uptake inhibitor, attenuated the choline-induced increase of plasma prolactin levels. These results show that choline increases plasma prolactin levels by activating muscarinic receptors via presynaptic mechanisms.  1997 Elsevier Science Ireland Ltd. Keywords: Choline; Acetylcholine; Prolactin; Atropine; Mecamylamine; Hemicholinium-3 Choline, a precursor of the neurotransmitter acetylcholine (ACh), increases ACh synthesis [19] and release [3,4,8, 9,16,18], enhancing cholinergic transmission. Previous stu- dies have shown that choline-induced increase of ACh synthesis and release produces functional changes in post- synaptic neurons and endocrine cells to those received cho- linergic inputs [1,6,13,14,15,17]. Considerable evidence shows that cholinergic drugs, including nicotine and phy- sostigmine [5,11,12], increase plasma prolactin levels. In the light of these studies we postulated that choline might also affect prolactin secretion. Therefore, the present study was designed to determine if intracerebroventricular (i.c.v.) injected choline increases plasma prolactin levels in con- scious rats. Male Wistar rats (Experimental Animals Breeding and Research Center, Uludag University Medical Faculty, Bursa, Turkey) weighing 280–350 g were used in all experi- ments. The rats were housed four per cage under controlled conditions (20–24°C with a 12 h light/dark cycle) with free access to food and water. The following experimental pro- tocols were approved by the Animals Care and Use Com- mittee of Uludag University. Under light ether anesthesia, a catheter (PE 50 tubing) filled with heparinized saline (400 U/ml) was inserted into the left common carotid artery for repetitive blood sam- pling. For i.c.v. injections of drugs, a burr hole was drilled through the skull 1.5 mm lateral to mid-line and 1.0 mm posterior to bregma and tip of a 23 gauge stainless steel guide cannula was lowered 4.5 mm below the skull surface and fixed with acrylic cement. Following surgery, rats were placed in individual cages and allowed to recover from anesthesia for approximately 3 h. During this period the rats remained calm and without evidence of pain. All experiments were performed between 1400–1600 h. After the recovery period, an injection cannula (25 gauge, 11.5 mm stainless steel tubing) was inserted through the guide cannula for i.c.v. injection. The injection cannula was connected to a Hamilton microsyringe (50 ml) by poly- ethylene tubing (20–30 cm) filled with saline or saline con- taining the desired dose of the drug of interest. Choline, atropine, mecamylamine and hemicholinium-3 (HC-3) were freshly prepared and were dissolved in saline (0.9% NaCl) solution. Drugs were then infused slowly over 6–8 s. The injection volume was monitored by observing the movement of an air bubble placed in the polyethylene tub- ing. The volume of solutions injected into the cerebral ven- tricle was 10 ml. Correct placement of the intraventricular Neuroscience Letters 232 (1997) 79–82 0304-3940/97/$17.00  1997 Elsevier Science Ireland Ltd. All rights reserved PII S0304-3940(97)00580-6 * Corresponding author. Tel.: +90 224 4428804; fax: +90 224 4428189.