Date of Award


Document Type

Campus Access Dissertation

Degree Name

Doctor of Philosophy (PhD)


Developmental and Brain Sciences

First Advisor

Susan Zup

Second Advisor

Richard Hunter

Third Advisor

Zsuzsa Kaldy


The presence of the Y chromosome in males results in the production of gonadal hormones that direct the development of the body into a male phenotype, while the absence of the Y chromosome in females allows a default process to shape the body into a female phenotype. This basic developmental process also extends into the brain: myriad sex differences in the brain and behavior can be traced back to these early hormone events. This dissertation explores the process of sexual differentiation in two nuclei within the rat hypothalamus—the paraventricular nucleus (PVN) and the sexually dimorphic nucleus (SDN-POA)—as well as two sexually dimorphic behaviors: juvenile social play and the propensity for drug abuse. We present evidence that the developing brains of males and females respond differently to serotonin. Specifically, increasing serotonin with 5-methoxytryptamine (5-MT) during the pre- and early post-natal period results in maladaptive cellular changes in the PVN of males that may hinder normal development of the PVN, and that also seem to disrupt juvenile play behavior. Increased developmental serotonin with 5-MT or DOI also feminizes the volume of the SDN-POA of males, but not a calbindin-immunoreactive subpopulation of cells within the SDN-POA. Analysis of SDN-POA mRNA suggests that the population of cells within the SDN-POA that do respond to serotonin may include cells that express corticotrophin releasing factor and the estrogen receptor beta. In addition, sex differences in some adult behavioral responses to cocaine, such as locomotor activity, rearing, and jumping, are organized by perinatal testosterone exposure, while other behaviors, such as conditioned reward, are not. In total, this dissertation shows that the brains of males and females are different in their response to early serotonin signaling and to drugs of abuse, and adds to a growing body of literature that the process of sexual differentiation in the brain is cell-type specific and results in sex differences that are not fully binary—they are each derived from separable mechanisms that allow for the brain to ultimately become a mosaic of both male and female features.


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