Joan I. Morrell, Ph.D.

Professor II, Center for Molecular and Behavioral Neuroscience

Rutgers University

Link to Publications on Pubmed

Overview

Presently the laboratory has two areas of focus. We study the impact of drugs of abuse on maternal motivation in maternal rats, and the impact of drugs of abuse on the normal development of preweanling rats.  These animal models are used with the intention that they contribute to our understanding of how the integrated patterns of brain function ultimately yield complex behavioral sequences. Information gathered in the studies of animal models validly generalizes to the fundamental neurobiological underpinnings of parental behavior, drug dependency, and preadolescent behaviors and their consequences in humans

Maternal Motivation and Drugs of Abuse

Maternal motivation is an important and understudied aspect of maternal behavior. My studies assess maternal motivation by using conditioned place preference, in a unique a paradigm that requires the choice of a chamber associated with drugs or a different chamber associated with pups. Novel and significant findings we have gathered include:    

1. In the choice paradigm, most postpartum females preferred pup-associated cues early in the postpartum period, whereas later in the postpartum period most preferred cocaine-associated cues (Mattson et al, 2001, 2003; Seip et al 2007, 2008).   
   
   
   
2. We have discovered that the incentive salience of cocaine is remarkably stable across the postpartum period.   Further we now know that a decrease in the motivation of the female towards pups is responsible for the change from preference for pup-associated cues to preference for cocaine-associated cues in most females during the late postpartum period in the choice paradigm (Wansaw et al 2008; Seip et al 2007, 2008).     
   
   
   
3. Maternal motivation (appetitive phase of the behavior) and expression of the active components of maternal behavior (consummatory phase of the behavior) are separable responses.  A further and key inference is that neural circuits regulating these two phases of maternal behavior are at least partially separable.  
   
   
   
   
4. Neuronal activation the motivational processes was revealed when we identified the brain regions where neurons are activated by of females that prefer either cues associated with pups or cues associated with cocaine by using c-Fos or cocaine- and amphetamine-regulated transcript (CART) immunocytochemistry. These data were the first to show that the medial prefrontal cortex is involved in maternal motivation, and confirmed and expanded our understanding of the role of the nucleus accumbens and medial preoptic area in both drug and maternal motivation.  This work also distinguished the different populations of neurons in the accumbens and prefrontal cortex that are activated by motivational processes associated with pharmacological versus natural rewards (Mattson and Morrell, 2005; Morrell et al, 2007; Pereira et al 2008).

Preweanling Rats Meet the Drug Challenge

This model offers important information both about the infant rat in the natural setting and in behavioral paradigms that examine the impact of neuropharmachological agents of potential clinical utility. Young mammals are not simply smaller versions of adults, and the impact of pharmacological treatments on their central nervous system can only be understood in the context of their developing nervous system, and its behavioral capacity. The preadolescent rats we use in these studies offer an important and understudied preclinical model vital to treatment of the tragedy of preadolescent substances abuse and the opportunity to use pharmaceuticals to treat mental health problems in our children.          

In this area, work focuses on the behavioral capacities and cocaine responses of the infant rats (12-30 days old).  A comprehensive series of studies on the activity and anxiety responses as well as specific stimulus responses in the late infant include their responses to drug (cocaine) challenge (Smith and Morrell, 2007; 2008). These studies demonstrate significant capacity for independent exploration of the environment based on a diurnal rhythm that is different from the adult in key features, an equivalent energy capacity to the adult for locomotor activity and wheel running, and notably greater willingness to explore anxiety-provoking locations than found in the adult. Interestingly, near-adult levels of neophobia for new foods are present in the postnatal infant. In marked contrast, however, these infants are much more willing to engage with specific stimuli (social stimuli, objects, or prey) that offer interactive capacity.

Human drug experimentation begins during late childhood and early adolescence, a critical time in physical and CNS maturation, when the immature CNS is vulnerable to the long-term effects of psychoactive drugs.  Few preclinical animal studies have investigated responses to such drugs in a developmental stage equivalent to late childhood of humans.  We used a rodent model to examine behavioral responses of female Sprague-Dawley late preweanling and adult rats during acute and repeated exposures to a low dose of cocaine.  Results show that after cocaine injection, preweanling rats (18-21 days old) have locomotor responses that differ from adults, but after postnatal day 22, the responses are indistinguishable from adults even though rats are still not weaned.  Before day 22, locomotor effects of cocaine differ from those in adults in three ways: at day 18 preweanlings are active for a longer time after cocaine injection; preweanling activity peaks more rapidly after subcutaneous administration; and after only three injections of cocaine, a tolerance-like pattern is seen in preweanlings whereas an emerging pattern of sensitization to cocaine is seen in adults.  The behavioral patterns of this age group offer a preclinical model of the early effects of drugs of abuse.