.... 1 J I . Brain R~search, 607 (1993) 177-184 C 1993 Elsevier Science Publishers B.V. All rights reserved 0006-8993/93/$06.00 1 --:- ,. BRES 18657 Potentiation by choline of basal and electrically evoked acetylcholine release, as studied using a novel device which both stimulates and perfuses rat corpus striatum Steven A. Farber, Udo Kischka, David L. Marshall and Richard J. Wurtman ,Depanm~nt of Brain and COgnitiL'~Scimces, MQSSQchusmsJnstitut~of T«hnology, Cambridge, MA 02139 (USA} (Accepted 20 October 1992) J(q words: Acetylcholine: Choline: Dopamine: Electrical stimulation: Microdialysis; Neostigmine: Striatum We examined the release of acetylcholine (ACh) and dopamine (DA) using a novel probe through which striatal neurons could be both superfused and stimulated electrically in both anesthetized and freely moving awake animals. Optimal stimulation parameters for eliciting ACh release from cholinergic neurons differed from those required for eliciting DA release from dopaminergic terminals: at 0.6 ms pulse duration. 20 Hz and 200 p.A. ACh release increased to 357:t 30% (P < o.on of baseline and was blocked by the addition of tetrodotoxin (1TX). Pulse durations of 2.0 ms or greater were required to increase DA release. Unlike ACh release. DA release showed no frequency dependence above 5 Hz. The maximalevoked releases of ACh and DA were 556:t94% (P < O.OJ) and 254:t38% (P < 0.05) of baseline. respectively. Peripheral administration of choline (Ch) chloride (30-120 mg/Icg) to anesthetized animals caused dose-related (r - 0.994. P < o.on increases in ACh release: basal release rose from 117:t7% to 141:t5% of initial baseline levels (P<O.05) and electrically evoked ACh release rose from 386:t 38% to 6OO:t34% (P < o.on in rats given 120 mg/Itg. However. Ch failed to affect basal or evoked DA release although neostigmine no 110M) significantlyelevated basal DA release (from 36.7 fmol/IO min to n.5 fmol/IO min: P < 0.05>. In awake animals. Ch (120 mg/kg) also elevated both basal (from 106:t7% to 154:t 17%: P < 0.05)and electricallyevoked (from 146:t 13 to 262:t 19~: P < o.on ACh release. These experiments demonstrate that ACh and DA release can both be reliably evoked from rat striatum and that an intraperitoneal (i.p.) injection of Ch can increase both basal and evoked striatal ACh release. INTRODUCTION Numerous studies have applied the technique of in vivo microdialysis29 to investigate the regulation of DA and ACh release from rat striatum1.2.4.6.7.23.2S. Such studies have sometimes used high potassium concen- trations within the perfusate to evoke neurotransmitter release by depolarizing neurons in the vicinity of the probe2.23.2S. While this technique is useful for releasing large amounts of neurotransmitter 9, it is less physio- logic than providing short-duration electrical pulses. Moreover. high potassium concentrations can produce permanent alterations in synaptic transmission14 and can. with subsequent challenges, release diminishing quantities of AChJ9. The present study used a novel custom-made micro- dialysis probe. containing a tungsten stimulating elec- trode, to depolarize neurons electrically in the direct vicinity of the microdialysis membrane. This treatment was found to produce more than a fourfold increase in ACh release and similar responses could be elicited by subsequent stimulations. The use of the hybrid probe enabled us to characterize the electrical parameters that affect both ACh release from striatal intemeurons and DA release from nigrostriatal terminals. After establishing that ACh release could be reliably evoked and entirely suppressed by the infusion of TIX. we explored the effect of exogenous Ch on basal and electrically evoked ACh release. Previous studies had established that dietary Ch could enhance tissue ACh and Ch levels in various regions of rat brain3.1S and that addition of Ch to superfused neurons could produce dose-related increases in basal and evoked ACh release from striatal slicesI7.28.However. studies of the effects of Ch on basal ACh from rat striatum, as assessed by in vivo microdialysis, have provided contra- C01WspotIIieru:~: RJ. Wunman. Department of Brain and Cognitive Sciences. Massachusetts Institute of Technology. Cambridge. MA 02139. USA. fax: (J) (617) 253-6882. ----