The role of dopamine in normal and abnormal behavior has been the subject of a massive amount of research since dopamine was first shown to be linked to Parkinson's disease, schizophrenia, and motivation and reward mechanisms in the 1960s and 1970s. Based on the number of publications that have dealt with it, dopamine is arguably the most important or at least most intriguing neurotransmitter in the brain. It has been implicated in a very large number of behaviors, with a theoretical ubiquitousness that has led it to be facetiously referred to as “everyman's transmitter because it does everything” (Koob, cited in Blum, 1997).

There is one general conclusion regarding dopamine and behavior that a clear majority of neuroscientists would agree on: dopamine enables and stimulates motor behavior. Increased dopamine transmission, at least up to a certain point, leads to behavioral activation (e.g. increased locomotion, vocalizations, and movements of the face and upper-extremities) and speeds up motor responses; conversely, diminished dopamine transmission leads to akinetic syndromes, including in the extreme mutism (Beninger, 1983; Salamone et al., 2005; Tucker and Williamson, 1984). One of the distinguishing features of excessive dopamine in the brain is motor behavior known in lower animals as “stereotypy” – constant, repetitive movements that would resemble compulsive behavior in humans (Ridley and Baker, 1982). A dramatic example of dopamine's role in motor behavior is the “stargazer” rat, which has very high dopamine levels and activity levels four to five times those of normals (Brock and Ashby, 1996; Truett et al., 1994).

If one believes that human evolution – especially in its intellectual aspects – did not rely exclusively or even largely on brain size and genetic transmission, then human evolution has never ceased. Hence, it would be incorrect to assume that all genetically modern humans and societies have the same neurochemistry and therefore the same intellectual abilities, personalities, goals, and propensity toward mental disorder. In particular, there is reason to believe that levels of dopamine are now much higher in members of modern industrialized societies than in more primitive societies. This chapter will focus on two major historical epochs – the transition from the hunter-gatherer societies to the ancient civilizations and the dramatic expansion of the dopaminergic consciousness and lifestyle in the twentieth century. In so doing, this chapter will highlight the role of influential individuals in history who have manifested dopaminergic traits and behaviors and played important roles in shaping our modern dopaminergic world.

The transition to the dopaminergic society

Despite a certain degree of technical proficiency, Neanderthals and even modern humans for their first 100,000 years appear to have lacked the generativity and pervasive “off-line” thinking capabilities of later humans. Once the prehistoric cultural “Big Bang” had progressed to its final stages and the last great Ice Age began to recede around 20,000 years ago, intellectual evolution proceeded at a rapid pace, with seemingly but an instant required from the Neolithic Era and the beginnings of agriculture to the ancient civilizations and the Copper, Bronze, and Iron Ages.

Between two and three million years ago, a small creature hardly larger than a pygmy chimpanzee but with a much larger brain relative to its body weight began a remarkable journey. The initial part of that journey didn't involve much by today's standards, merely the ability to scavenge and possibly chase-hunt the creatures of the sub-Saharan African savannahs, to make some rather modest stone-flaked tools for that purpose, and eventually to migrate over the African and possibly the Eurasian land mass. This little creature, arguably our first unequivocally human ancestor, was known as Homo habilis (“domestic” man). How the modest abilities of this first human emerged and were transformed into the prodigious human achievements and civilization that exist today is arguably the most important scientific mystery of all. The solution to this mystery will not only help to explain where and why we evolved as we did – it will additionally shed light on how we may continue to evolve in the future.

But, first, some basic questions must be asked, including: what is human nature and what is the basis of it? How much of human nature is related to our genes? Is human nature related to the size and shape or lateralization of our brain? How did human nature evolve? Although our hairless skin and elongated body make our appearance quite different from our primate cousins, it is not our anatomy but our unique brain and behavior that most people consider special.

It is customary, albeit limiting, to view human brain evolution in terms of the events leading up to genetically and anatomically modern humans, now believed to be approximately 200,000 years ago. All subsequent changes in humans are attributed to the effects of “culture,” and human “history” is relegated to even more modern events beginning with the formation of agricultural societies. If, however, the expansion of dopamine was not due mainly to genetically mediated changes in our neuroanatomy but rather to epigenetic changes in our neurochemistry, then the physical brain evolution of modern humans has continued all the way to the present. This chapter will focus on the evolution of the dopaminergic mind leading up to, and including, the cultural explosion in Homo sapiens that has been termed the “Big Bang” (Mithen, 1996), which occurred first in Southern Africa between 70,000 and 80,000 years ago and later appeared in Europe around 40,000–50,000 years ago, while Chapter 6 will focus on the changes in the dopaminergic mind since the dawn of history. I will highlight two major events in human evolution – the evolution of the “protodopaminergic” mind beginning around two million years ago and the emergence of the later dopaminergic mind with its distinctly human intellectual abilities less than 100,000 years ago. First, however, it is necessary to describe further the contribution of epigenetic influences to inheritance, given the crucial role they appear to have played in our intellectual evolution.

In this chapter, I will attempt to briefly describe what dopamine consists of, where it is located in the brain, and what basic actions it has. Much of this information will be applied in Chapters 3 and 4 with reference to the roles of dopamine in normal and abnormal behavior.

The neurochemistry of dopamine

Like all brain neurotransmitters, dopamine is a chemical that contains most of the important building blocks of life – carbon, hydrogen, oxygen, and nitrogen. It is a phylogenetically old transmitter, found in primitive lizards and reptiles existing tens of millions of years ago. The chemical structure of dopamine is shown in Figure 2.1. Dopamine is known as a catecholamine, which derives from its having a catechol group and an amine group that are joined by an additional carbon pair. The catechol group consists of a hexagonal benzene (carbon-bonded) ring with two hydroxyl (oxygen and hydrogen, or OH) groups. The amine group is a molecule comprised of an atom of nitrogen and two atoms of hydrogen (NH2). The chemical structure of dopamine is not all that special, in that its atoms and molecules derive from some of the most common elements on Earth and especially those found in organic compounds. Carbon, in particular, is essential to life on Earth, partly because it so readily makes bonds with other biological molecules.

The “hyperdopaminergic” syndrome

Despite the many positive dopaminergic traits described in Chapter 3, the dopaminergic story has another, darker side. Whereas too little dopaminergic transmission in disorders such as Parkinson's disease and phenylketonuria is debilitating to motor and intellectual functioning, excessive dopamine activity in one or more brain systems has been implicated in an even larger number of prominent neuropsychological disorders – including attention-deficit disorder (also known as attention-deficit/hyperactivity disorder when accompanied by hyperactivity), autism, Huntington's disease, mania (also known as hypomania and bipolar disorder when it alternates with depression), obsessive-compulsive disorder, schizophrenia, and Tourette's syndrome. Other hyperdopaminergic disorders include substance abuse (highly associated with attention-deficit/hyperactivity disorder and bipolar disorder) and stuttering (linked to Tourette's syndrome). All of the hyperdopaminergic disorders are closely related to one another in terms of their co-morbidities and symptoms, and more than one set of hyperdopaminergic symptoms are surprisingly often found in the same individual (e.g. autism with obsessive-compulsive and Tourette's features; mania with schizophrenic-like psychosis and obsessive-compulsive behavior) or within families. The various hyperdopaminergic disorders also are highly amenable to the same pharmacological interventions (principally D2 receptor-blocking drugs). In fact, drugs that decrease dopamine levels in either the brain generally or in a specific system (e.g. the ventromedial one) are the main or secondary pharmacological treatment of choice in every hyperdopaminergic disorder except for Huntington's desease.

Dopamine excess contributes to the motor symptoms (e.g. hyperactivity, tics, motor stereotypies), delusions and hallucinations, and social withdrawal found to varying degrees in the above disorders.

General aspects of D1 receptors

In the presence of a D2 antagonist, the binding of [3H]dopamine to rat brain sections is very selective for dopamine D1 sites, and is entirely displaced by low concentrations of the prototypic D1 antagonist Sch 23390 (Herve et al. 1992). However, the D1 receptors linked to adenylate cyclase may constitute a subset of the binding sites for [3H]Sch 23390 (Andersen & Braestrup 1986). In the absence of sodium ion, two affinity states of dopamine D1 receptors for dopamine can be distinguished. The high-affinity state of the receptor, which is sensitive to the presence of GTP, seems to constitute about one half of the total binding in membranes prepared from bovine caudate (Seeman et al. 1985). Likewise, increasing concentrations of a D1 agonist displace [3H]Sch 23390 from D1 receptors in human caudate in a biphasic manner, revealing approximately equal proportions of D1Low and D1High states of the receptor. In contrast, others report the fraction of dopamine D1 receptors in rat cryostat sections in a high-affinity state for dopamine to be only 20%, versus 77% for D2 receptors (Richfield, Penney, & Young 1989).

The regulation of dopamine D1 receptor expression in living brain is poorly understood. Steroid hormones play a role, since the striatal binding of [3H]Sch 23390 in female rat decreased following ovariectomy, and varied across the estrus cycle (Levesque, Gagnon, & Di Paolo 1989).