Prenatal cocaine exposure increases serotonergic inhibition of electrically evoked acetylcholine release from rat striatal slices at adulthood

• Published in: Synapse (New York, N.Y.) N.Y.), 2000-04, Vol.36 (1), p.1-11
• Main Authors: Bolaños, Carlos A., Trksak, George H., Glatt, Stephen J., Jackson, Denise
• Format: Article
• Language: English
• Subjects: acetylcholine; Acetylcholine - metabolism; alpha-Methyltyrosine - pharmacology; Animals; Biguanides - pharmacology; Cocaine - toxicity; dopamine; Dopamine - physiology; Dopamine Uptake Inhibitors - toxicity; Electric Stimulation; Enzyme Inhibitors - pharmacology; Estrogens - blood; Estrus - physiology; Female; In Vitro Techniques; Male; Neostriatum - drug effects; Neostriatum - metabolism; Neostriatum - physiology; Neurons - drug effects; Neurons - metabolism; Pregnancy; prenatal cocaine; Prenatal Exposure Delayed Effects; Progesterone - blood; Rats; Rats, Long-Evans; release; Serotonin - physiology; Serotonin Receptor Agonists - pharmacology; serotonin receptors; Sex Characteristics; striatum
• ISSN: 0887-4476; 1098-2396
• DOI: 10.1002/(SICI)1098-2396(200004)36:1<1::AID-SYN1>3.0.CO;2-F

This study tests the hypothesis that prenatal cocaine (pCOC) exposure (20 mg/kg, bidaily from embryonic days 15–21) modifies 5‐HT3 receptor regulation of electrically‐evoked [3H]acetylcholine (ACh) overflow from adult male and female (proestrus, diestrus) rat striatal slices. Also, the influence of endogenous dopamine (DA) on serotonin (5‐HT) regulation of ACh overflow was determined by assessing the effects α‐methyl‐para‐tyrosine (AMPT) pretreatment or sulpiride. Phenylbiguanide (PBG, 5‐HT3 agonist) superfusion dose‐dependently inhibited ACh overflow in all groups except the diestrus pCOC group in which there was an enhanced sensitivity to PBG. PBG (10, 30, and 60 μM) produced greater effects in the pCOC male than in the prenatal saline (pSAL) group. The pCOC male group also exhibited greater sensitivity to PBG (30 and 60 μM) than the pCOC proestrus group. PBG inhibition of ACh overflow was comparable in the pSAL male and female (proestrus) groups. PBG inhibition of ACh overflow was greater in the pCOC diestrus group than in the pCOC proestrus (10, 30, and 60 μM), the pSAL diestrus (10 and 30 μM), and the pCOC male (10 μM) conditions. In slices from untreated rats superfused with 30 μM PBG, AMPT pretreatment (68% DA loss) reduced inhibition of ACh overflow, and 1 μM sulpiride increased ACh overflow. ICS205‐930 (5‐HT3 antagonist) reduced effectiveness of PBG indicating 5‐HT3 receptor specificity for PBG. In summary, pCOC exposure enhances modulatory effects of 5‐HT (via 5‐HT3 receptors) on striatal ACh release in male and females rats and the inhibitory actions of 5‐HT3 receptors are mediated by DA. Synapse 36:1–11, 2000. © 2000 Wiley‐Liss, Inc.