Developmental Brain Research, 24 (1986) 193-202 193 Elsevier BRD50323 Pharmaco-Ontogeny of Reward: Enhancement of Self-Stimulation by D-Amphetamine and Cocaine in 3- and 10-Day-Old Rats GORDON A. BARR and TED LITHGOW Biopsychology Program, Department of Psychology, Hunter College of the City University of New York, New York and Department of Psychiatry, Albert Einstein College of Medicine, Bronx, NY (U.S.A.) (Accepted July 9th, 1985) Key words: self-stimulation - - intracranial self-stimulation (ICSS) - - reward - - D-amphetamine - - cocaine - - limbic system - - medial forebrain bundle - - nucleus accumbens - - monoamine - - development - - ontogeny - - neonates Electrodes were implanted in various forebrain sites in 3- and 10-day-old rat pups that were allowed to nudge a pole for electrical stimulation of those areas. After 5 h pups were injected with amphetamine, cocaine or saline and the change in responding noted. Both stimulants, at relatively high doses, enhanced responding on the pole that produced stimulation to a greater extent than responding on a non-active pole. At lower doses, responding on both the active and inactive poles were enhanced equally. These effects lasted 2-3 h. Histological analyses showed that the most sensitive loci that were consistently enhanced by these stimulants included the medial fore- brain bundle, nucleus accumbens, anterior olfactory nucleus and olfactory tubercle. The results suggest that the biological mecha- nisms by which these drugs enhance self-stimulation in adult animals are present in neonates. INTRODUCTION The rat is born both behaviorally and neurological- ly immature, but nonetheless is capable of learning. While the mother largely controls the feeding bouts 32 the pups must approach, attach to and suck from the dam's nipple. Recently, it has been demonstrated that pups learned new associations while sucking on the nipple; pups preferred the diet fed their moth- er 7.14 and a novel odor paired with milk delivery6. The simple opportunity to suck, whether accompa- nied by milk or not, reinforced their behaviorl, 26. Furthermore, pups fed independently, unattached to the nipple 17-j9.52, learned an operant for milk infused into their mouth 23 and oriented towards odors that had been previously paired with milk infusions24, 25. Despite the demonstrations of the impressive abili- ties of neonates to learn, little is known of the physio- logical and neurochemical bases of reinforcers in the infant animal. Some studies do exist: 5- to 6-day-old domestic chicks 3, 4- to 5-day-old beagle dogs 5 and 3- and 7-day-old rat pups 35.37 responded to stimulation of the medial forebrain bundle (MFB) of the lateral hypothalamus and to stimulation of other forebrain sites, including the nucleus accumbens, frontal cor- tex, bed nucleus of the stria terminalis and piriform cortex 35. These sites corresponded well to sites sup- porting self-stimulation in adults and argue for devel- opmental continuities in the neural bases of reward. Pharmacological studies have shown ampheta- mine to be active and possibly reinforcing to the neo- nate. Pups attached to a nipple that was devoid of normal olfactory cues needed for attachment in the presence of an odor that had been previously paired with amphetamine 41 or stroking 49. It was proposed that activating stimuli including amphetamine served as reinforcers for the novel odors. Amphetamine also enhanced milk intake in young non-deprived pups 9,30,51 (see also ref. 45). While the neurochemical actions of these behavioral effects of amphetamine have not been studied, the drug did increase activity in the nigrostriatal dopamine system at these early ages22. Because amphetamine and to a lesser extent co- Correspondence: G.A. Barr. Department of Psychiatry, Albert Einstein College of Medicine, 130(IMorris Park Avenue, Bronx, NY 10461, U.S.A. 0006-8993/86/$03.50 © 1986 Elsevier Science Publishers B.V. (Biomedical Division)