D1 agonist CY208–243 attenuates the pattern electroretinogram to low spatial frequency stimuli in the monkey A. Peppe a , A. Antal b , M. Tagliati d , P. Stanzione a,c , I. Bodis-Wollner e, * a Department of Neurology SUNY-HSCB, IRCCS S.Lucia Via Ardeatina 306, 00179, Rome, Italy b Department of Physiology, Szrent Gyo ¨ rgyi Albert 2 University, Szeged, Hungary c Clinica Neurologica, Universita ` di Tor Vergata, Rome, Italy d Department of Neurology, The Mount Sinai Medical Centre, New York, NY, USA e Department of Neurology, State University of New York Health Science Centre-HSCB, 450 Clarkson Avenue, Brooklyn, New York, NY 112011, USA Received 12 June 1997; received in revised form 5 December 1997; accepted 9 January 1998 Abstract We investigated whether or not the D1 agonist, CY 208–243, affects the spatial tuning function of pattern electroretinogram (PERG). Two lightly anaesthetised monkeys were studied before and after CY 208–243 or placebo administration. The results show that the PERG response to 0.5 cycles/degree (c/d; coarse), but not to 2.3 c/d (medium) spatial frequency stimuli dis- appears following systemic administration of this drug. Since previous results show that D2 blockers attenuate the PERG only above 2.3 c/d, foremost the peak of the normal spatial frequency response function, the current results suggest that dopamine itself, via D1 receptors, may be responsible for the low spatial frequency decline of normal spatial PERG tuning function. We infer that the synergistic activation of D1 and D2 receptors is needed to shape the spatially tuned primate ERG. 1998 Elsevier Science Ireland Ltd. Keywords: Retina; Tuning function; Spatial frequencies; Dopamine; D1 agonist; Monkey Dopaminergic receptors are present in the retina of mon- keys and humans [12,22]. Both D1 and D2 receptors have been reported in the inner and outer retina of both species [4,17]. Although other subclasses of dopaminergic receptors also exist in the central nervous system and retina, at present their properties and functional roles in retinal processing are less understood than those of D1 and D2 receptors. Increase of major positive wave P50 of transient pattern electroreti- nogram (PERG) reported in Parkinson’s disease (PD) patients [14,18] have been attributed to dopaminergic defi- ciency since this PERG increase can be at least partially reversed by L-Dopa [18]. It is known that PERG amplitude to medium spatial frequency stimuli is larger than to coarser and finer stimuli. This is called spatial frequency (SF) tun- ing. It is also known that a tuned spatial frequency PERG response function is generated by ganglion cells [8]. Tuning in dopaminergic deficiency states can be evaluated by tak- ing the amplitude ratio between the responses at peak and at low spatial frequency stimulation [21]. A reduction of PERG responses to medium spatial frequencies of stimula- tion (loss of tuning), similar to contrast sensitivity changes observed in PD patients [2], can also be achieved by D2 antagonist administration in humans [19] and in monkeys [21]. From these studies, it is apparent that D2 receptors play an essential role in spatial frequency response function of the PERG in humans and monkeys. Less is known about the functional role of D1 receptors in retinal processing in primates. D1 activation has been reported to close gap junc- tions of horizontal cells [15,16] in turtles and in other lower vertebrates such as goldfish as well as between amacrine cells in mammalian retina [5,6]. However the effect of clos- ing horizontal gap junction on the centre-surround organi- sation of subsequent neurons, including ganglion cells, is not known with precision. It is thought that horizontal cells are mostly important for the surround organisation. Hence, altered horizontal cell contribution may change the sur- round organisation of ganglion cells [9,10]. Whether or not a change of horizontal cells performance affects the Neuroscience Letters 243 (1998) 5–8 0304-3940/98/$19.00 1998 Elsevier Science Ireland Ltd. All rights reserved PII S0304-3940(98)00068-8 * Corresponding author. Box 1213.