The Hypothalamus and Addiction

United States

Introduction

Co-chairs: Karen Skinner, Ph.D. and Jonathan Pollock, Ph.D.

On July 10, 2001, NIDA sponsored a workshop entitled "The Hypothalamus and Addiction." The purpose of the meeting was to discuss the extent to which gene expression studies in the hypothalamus may inform biological studies on the anatomy and function of the hypothalamus in varying "states" including addiction. The workshop brought together leading experts interested in the hypothalamus from a variety of research perspectives. Their expertise included molecular biology, the anatomy and development of the hypothalamus, and the role of the hypothalamus in sleep, appetite, addiction, and mental health. The workshop's agenda included a few brief presentations to stimulate discussion. They covered a range of topics including: (1) the functional significance of the hypothalamus from an evolutionary perspective; (2) the utility of studying gene expression in the hypothalamus to identify neuronal cell types and their interactions; (3) current perspectives and hypotheses regarding the role of the hypothalamus in addiction; (4) applications of molecular biology to specific neuronal tracing; (5) identification and quantification of low expression genes; (6) acquisition of spatial information about gene expression; (7) advances in understanding the complexity of hypothalamic connections and gene expression; and (8) the extensive challenges associated with high throughput transfer of gene expression data to a 3-dimensional atlas in a practical, informative and correct manner.

Conclusions

• Compelling evidence exists that the hypothalamus impacts upon addiction.
• Studies elucidating the functional neuroanatomy of the hypothalamus -- including cell types and their control states -- would be valuable for addiction research and other areas of study. Such studies might also serve as prototypes for similar analysis of other brain regions.
• The hypothalamus is an excellent brain region for studying functional neuroanatomy because of its diverse cell types, its rich peptide content, its evolutionary conservation, and its role in mediating homeostasis and basic behaviors.
• Model organisms may be useful in simplifying such studies and in acquisition of samples.
• Establishing an understanding of baseline functional neuroanatomy at the cellular level is critical to understanding plasticity and transition among states.
• A wide range of existing and emerging tools and techniques may be applied to studies of functional neuroanatomy of the hypothalamus.

Recommendations

• Studies of the functional neuroanatomy of the hypothalamus should be unified at the cellular level
• Cell-based studies should address the following questions:
  • How many different types of neurons and glial cells are present in the different nuclei of the hypothalamus?
  • What specifies them?
  • What genes do they express?
  • What do they respond to?
  • From where do they receive inputs?
  • Where do they project and what specifies the projections?
  • What effect does activation/inhibition of a neuron have on the organism?
• To best address these questions, a consortium of investigators sharing resources and information should be established.
• More than a standard database is needed. Data should be transformed into a knowledge base organized at the cellular level, which includes information about a cellÕs connections and gene expression profile. A knowledge base is needed from which computations can be made. A pilot study should be initiated to explore approaches to the development of such a knowledge base.
• To stimulate creative and innovative studies, and to accommodate advances in technology and understanding, many approaches to investigating the functional neuroanatomy of the hypothalamus should be undertaken .
• When possible, investigators interested in identifying cellular perturbations should consider the potential utility of the existing repertoire of animal models available for addiction research.