lkopeun Journal oj Phurtmucology, 76 ( I98 1) 42 I -425 Elsevier/North-Holland Biomedical Press 421 zyxwvutsrqp DOSEDEPENDENT FEEDING IN THE RAT FOLLQWING SUBSTANTIA MGRA ACETYLCHOLI zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA IVSTEMSEB-DE PHILIP WINN l and PETER REDGRAVE l * zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Depur t menr of Pqvhd~ , Unilwrsity of Hull HulI. IiU6 7RX. Engiund, und Sht#& SIO XN, En&xl l * Depurtnaenntoj P~vchclogv, University of Sheffield. Received 26 May 1981. revised MS received 2 October 1981, acceptedR October 1981 P. WINN attd P. REDGRAVE Dosedepen&nr feeding in the rut folluwing suhsruntiu nigru u~e!~i~holilirtesteru.~e hlockude, European J. Pharmaeol. 76 (198ll421-425. Microinjections of eserine sulphate into the substantia nigra elicited a dose-dependent increase in feeding, but not drinking, when both food attd water were freely available. This tqonse is strikingly similar to that elicited by other forms of cholinergic stimulation of the rat substantia ttigre. It is suggested that n&o-striatal dopamine neurones might receive a choline@ input within substantia nigra and play an important role in mediating this response. Acetylcholinesterase Substantia nigra Feeding Dopamine 1. lntr&uetion Work has been reported recently demonstrating that low levels of cholinergic stimulation within the substantia nigra elicit feeding behaviour in satiated rats (Winn and Redgrave, 1979). There are several points which suggest that this cholinergicalfy induced feeding might be mediated by nigro-striatal dopamine (DA) neurones. Firstly, Winn and Redgrave 11979) found that the amount consumed diminished with increasing distance of the microinjection site from the pars compacta region of substantia nigra, which is known to contain DA cell bodies (Ungerstedt, 1971). Sec- ondly, Taha and Redgrave ( 1980) demonstrated that low, non-sedative doses of the DA antagonist haloperidol abolished both the feeding elicited by low doses of carbachol and the oral stereotyped behaviour elicited by higher doses. Neurochemical and histochemical studies sup- port the hypothesis that an acetylcholine (ACh)/dopamine (DA) interaction exists within Acetylcholine Eserine the substantia n&a. Butcher and Marchand (1978) have shown that nigro-striatal DA neurones possess acetylcholinesterase (AChE) within their cell bod- ies and dendrites (as well as axons). Moreover, release of AChE from pars compacta DA neurone dendrites under physiological stimulation has also been demonstrated (Greenfield et al., 1980). As a result it might be suggested that AChE is released from the dendrites of DA neurones to inactivate ACh released from afferent terminals. In the past feeding has been elicited by in- tranigral administration of directly acting chol- inergic receptor agonists (Winn and Redgrave, 1979; Taha and Redgrave, 1980). The present ex- periment was designed to investigate whether a local potentiation of endogenous choline@ trans- mission within the substantia nigra by microinjec- tions of the AChE inhibitor eserine sulphate would constitute a sufficient condition for increasing food intake in satiated rats. * To whom all correspondence should be addressed: Depart- ment of Experimental Psychology, University of Cambridge. Cambridge, CB2 3EB. England. lnto each of six male black-hooded rats (PVG/C strain) (310-385 g), bilateral stainless (lo142999/8l/oooO-0000/$02.75 #? 1981 Elsevier/North-Holland Biomedical Press