Isidore Gormezano - US grants

Employing an animal (rabbit) model, our broad long-term objectives are to determine the effects of maternal drug abuse upon the offspring's long- term learning and memory. Specifically, we will determine whether daily maternal cocaine dosing from implantation to parturition will produce long-term deficits in the maturing offspring in the absence of morphological abnormalities. Collateral measures of the frequency of premature deliveries and stillbirths, and the offspring's body weight and CNS morphology will be taken to determine more general influences of prenatal cocaine exposure and the nutritional deficits attendant to drug exposure through the use of a yoked control experimental design. In pursuit of these objectives, we propose to undertake three overlapping, yet distinct, series of investigations. First, we will undertake detailing maternal cocaine's long-term effects on the maturing offspring's sensory, motor, and associative learning processes. Second, we propose to delineate the effects of maternal cocaine on the maturing offspring's short- and long-term memory. Third, we will seek to specify maternal cocaine's effects on stimulus reactivity; processing of visual, auditory and vibrotactile stimuli; habituation; and single-stimulus (nonassociative) learning processes. Our behavioral assessments will include Pavlovian paradigms involving aversive conditioning of the nictitating membrane response (NMR) and appetitive conditioning of the jaw movement response (JMR). The characteristics of these preparatIons have led to their achieving the status of model preparations for the study of associative learning and their neural and neurochemical substrates due principally to the absence of unconditioned (alpha) responses to stimuli used as conditioned stimuli (CSs), a low base rate of response occurrence, and the absence of any detectable pseudoconditioned or sensitized responses. In particular, we propose to employ a battery of procedures that we have developed for delineating drug effects on (a) associative, (b) nonassociative, (c) sensory, (d) motor components; (e) short-and long-term memory, and (f) neural substrates. In addition, we will determine cocaine's effects on: psychomotor development and nonassociative learning (i.e., single-stimulus) through habituation to the acoustic startle reflex.