The Neuropeptides Pharmacology Biochem&try and Behavior, Vol. 5, Suppl. l, pp. 3-9. ANKHO International Inc., 1976. Effects of Neonatal Cerebral Ventricular Injection of ACTH 4-9 and Subsequent Adult Injections on Learning in Male and Female Albino Rats TIMOTHY F. CHAMPNEY, TONY L. SAHLEY AND CURT A. SANI)MAN ~ 7he Ohio State University, Department of P,~vchologv, Columbu.~ 01t 43210 ('HAMPNEY, T. F., T. L. SAIII.EY AND C. A. SANDMAN. Lffi'cts of neonatal cerehral vent,'icular injecthm o.I,,tCTH 4 9 and subsequent adult injectkms on learning in male and female albino rats. PHARMAC. BIO('HEM. BEHAV. 5: S[PPI.. 1, 3-9, 1976. An investigation ot permanent deveh~t~mental effects of a potent, long acting A("TIt/MSlt 4- 10 analogue (Organon 2766) ~n adult passive avoidance performance and tJl" subsequent peripheral aduh injections of the same substance on visual ¢black and white) discrimination learning and reversal in a Thompson-Bryant box was conducted. A subqproblem analysis of visual and position preferences during rever~l was performed. No differences in passive avoidance performance or in original discrimination learning were obtained. Both infant and adult treatments enhanced reversal learning and visual orientation (proportion of responses to the previously positive stimulus). Infant treatment suppressed position orientation in males and enhanced position orientation in females. These effects were interpreted as indicating that ACTH-like peptides enhance attention to the relevant stimulus by a direct effect on the brain. Neuropeptides Attention Sex differences Adrenocorticotropic hormone ACTH analogues Discrimination learning Intracranial injections Melanocyt e-stimulating hormone CLASSICAL opinion suggested that adrenocorticotrophic hormone (A('TH) was active in the stress response of most animals and that melanocyte-stimulating hormone (MSH) changed the pigmentation of lower vertebrates and was merely vcstigeal in mammals, ttowever, recent evidence indicates that ACTtt, MSH and the centrally active amino acid sequence thai these two molecules share (MSH/ACTH 4 10) have observable behavioral consequences. Adminis- tration of these substances to adult rats has resulted in delayed extinction of active [3,23] and passive avoidance learning [17,32], delayed extinction of an appetitive task [31] and enhanced reversal learning of a brightness discrimination task [27,33]. The results have been inter- preted as indicating that the heptapeptide influences emotion or fear [2,231, memory [3], motivation [8.34], arousal [1], and attention [27,29]. In a series of recent studies, infant rats (age 2--7 days) werc given intraperitoneal injections of MSH and tested as adults with several behavioral tasks [30]. l-arly postnatal treatment of rats with MSH resulted in improved efficiency on a DRL-20 task, facilitated reversal learning, improved performance of the changed dimcnsion of an extra- dimensional shift in a visual discrimim~tion problem, and enhanced acquisition and hastened extinction of an active avoidance response. The results of the developmental studies also raised the possibility that the behavioral effects of these neuro- peptidcs were sex-dependent. The enhanced reversal learning appeared to be restricted to male animals. In another developmental study, increased gregariousness was most evident in females treated with MSH [30]. The current experiments were designed to explore further the sex and task dependency of early exposure to peptide hormone analogues. A longer acting derivative (A('TIt 4--9 analogue; Met-402, 8 D-Lys, 9 Phe-A('TII 4 t~, Organon 2766) purported to be many times more potent than A('Ttl, MSI-I or their other analogues was employed. To maximize the probability that the injections would effect the learning process by direct ('NS action, infant rats were injected intraventricularly, in addition, Experiment 2 was designed to assess the possibility thai rats prctreated with the A('TH4 C~analogue as infants would be sensitized to administration of this peptide derivative as adults. I-XPI-:IRIM E N'I" 1 M I.~THOI) Animals "Fen litters of rats delivered by polyparous mothers of the Sprague-Dawley lioltzman albino strain were housed with their mothers for the first three weeks postpartum in plastic maternity cages. At approximately 21 days of age the pups were weaned and housed in double metal cages in groups of 3 or 4. ('age mates were kept homogeneous with respect to litter, experimental group, and sex. Twenty-four hour constant diffuse lighting was used throughout the experiment. Seventy-seven rat pups were included in the experiment. ~Addrcss reprint requests to Curt A. Sandman, Department of l>',ychology, t'hc Ohio Slate University, 1945 N. [ligh St.,('¢~lumbus, Ohio 43210.