HT1A receptor knockout and anxiety

The converging lines of evidence that 5-HT1A receptor deficiency or dysfunction is involved in depression and anxiety disorders led to the genetic inactiva-tion of this receptor in mice (for reviews, see Lesch, 2005 Lesch et al., 2003). Htrla knockout (KO) mice show a complete lack of ligand binding to brain 5-HT1A receptors in null-mutant Htrla- - mice, with intermediate binding in the heterozygote Htr1a+ - mice. Importantly, a similar behavioral phenotype characterized by increased...

Behavioral Genetic Studies Of Anxiety And Depression

Behavioral genetic studies seek to understand the causes of variation in behavioral outcomes (for an introduction to the study of behavioral genetics, the reader is referred to Plomin, DeFries, McClearn, & McGuffin, 2001). These causes can be divided into those that are genetic and those that can be attributed to the environment. Indexing and quantifying these different sources of influence form the basis of most behavioral genetic designs (see Table 16.1). Through such twin and family...

Molecular And Functional Imaging Of The 5ht1a Receptor

While 5-HT1A receptors display high density in the limbic and cortical regions critically involved in mood regulation, PET studies have reported reduced 5-HT1A receptor binding in these regions in patients with major depression (Bhagwagar, Rabiner, Sargent, Grasby, & Cowen, 2004 Drevets et al., 1999 Sargent et al., 2000) and PD (Neumeister et al., 2004). Quite unexpectedly, Huang and colleagues (2004) demonstrated that 5-HT1A receptor binding in prefrontal cortex of persons who committed...

Grays Later Theory Of Anxiety

In the interest of saving space, we can now skip forward to the last comprehensive summary of this work on anxiety (Gray & McNaughton, 2000), entitled The Neuropsychology of Anxiety An Enquiry into the Functions of the Septo-Hippocampal System (2nd ed.). This work was published with Gray's one-time student Neil McNaughton, who was for many years his colleague collaborator and now is the heir apparent to this approach to anxiety and anxiety disorders. Although McNaughton was a major...

The Overlap Among Gray Eysenck And Cloninger

Gray (1986) argued that his dimensions of anxiety and impulsivity are not necessarily at odds with Eysenck's model of personality, and that his dimensions are at an approximate 45 rotation from Eysenck's dimensions of neuroticism and extraversion (Eysenck & Eysenck, 1985 Gray, 1970). This is illustrated in Figure 11.2, where anxiety harm avoidance runs diagonally across the two-dimensional plane defined by extraverted and neurotic, such that individuals with high harm avoidance fall within...

The Amygdala

Gray and McNaughton (2000, p. 1) began their book by commenting that current orthodoxy views the amygdala rather than the SHS as the key brain structure underlying anxiety. This comment refers to a large and elegant literature on the neural pathways involved in classical aversive fear conditioning especially the work of Davis (e.g., Davis, Walker, & Lee, 1999 Lang, Davis, & Ohman, 2000) and LeDoux (e.g., 1996 2000 and 2002, pp. 212-229), which emerged in parallel with Gray's own work. The...

Looking Forward

Despite the knowledge that heredity plays an important role in personality, mood, and anxiety, locating the quantitative trait loci for these complex traits and for disorders linked to them has proved difficult, although there have been some successes for example, Crohn's disease (Low et al., 2004 Peltekova et al., 2004 Stoll et al., 2004), schizophrenia (Berrettini, 2004 O'Donovan, Williams, & Owen, 2003 Riley, 2004), and asthma (Cookson, 2002 Cookson & Moffatt, 2002 Halapi &...

Neuroimaging Studies Of Sexual Response

Many neuroimaging studies have examined the neural correlates of fear, disgust, and other emotional states, but until recently little was known specifically about how the human brain responds to stimuli of a specifically sexual nature. Moreover, most of what is known about brain responses to sexual stimuli is limited to males, in part because it is generally easier to study male responses than female responses. These studies have primarily examined responses to erotic films or photographs, and...

General Summary And Comment

Jeffrey Gray's work focused on understanding anxiety at a behavioral, emotional, and neurobiological level. He brought to bear his extensive knowledge of animal learning theory and his expertise in behavioral neuroscience, with the two working synergistically in a manner that is rare. His brilliant insight that he could understand anxiety by defining it as the process affected by anxiolytic drugs productively guided his research throughout his career. This fundamental strategy provided a firm...

Human Correlational Studies

A large body of studies relates the enzyme monoamine oxidase (MAO) to sensation seeking and to forms of behavior and psychopathology that are related to sensation seeking. A review (Zuckerman, 1994) showed that levels of platelet MAO Type B (MAO-B) were inversely and significantly related to scores on the SSS General or Total scales in 9 out of 13 groups from 9 studies. The correlations were negative in 11 of the 13 studies. The median correlation was only -.24, a weak but relatively consistent...

Brain Responses To Emotional Stress Preliminary Evidence Of Sex Differences

In a series of studies, my colleagues and I have been examining the effects of emotional stress on drug craving and relapse in individuals who abuse substances. Emotional stress, or distress, commonly occurs in situations that are challenging or threatening, and it influences adaptive processes that require self-regulation or coping to regain control and attain desired goals Sinha, 2001 . Our initial findings with substance-abusing individuals and healthy volunteers has shown that emotional...

Mapping Extraversion In The Brain Deconstruction And Reduction

How can an individual-difference approach be applied to the study of extraversion or related personality traits in the brain Work to date has correlated responses on personality questionnaires with structural brain features Knutson, Momenan, Rawlings, Fong, amp Hommer, 2001 Onitsuka et al., 2005 neuroimaging of dopamine or serotonin function Knutson et al., 1998 Laakso et al., 2003 Suhara et al., 2001 and brain activation at rest Ebmeier et al., 1994 Johnson et al., 1999 Stenberg, Risberg,...

Orienting and Defensive Reflexes

Hypac Hormonal Axis

The first psychophysiological studies of sensation seeking used the orienting response OR to novel stimuli, as measured by the skin conductance response SCR to novel and repeated visual stimuli Neary amp Zuckerman, 1976 . There was no difference between high and low sensation seekers in basal levels of electrodermal measured arousal. Studies by other investigators, using SCR, heart rate, blood pressure, and electroencephalogram, did not yield any consistent differences in basal arousal...

And Frontal Brain Asymmetries

Evidence in favor of frontal brain asymmetries for emotion, personality, and psychopathology comes from numerous methodologies. Clinical case studies have shown that damage to the right hemisphere is associated with euphoric mood states, whereas damage to the left hemisphere results in dysphoric mood states Borod, 1992 Gainotti, 1972 . These findings parallel those for patients undergoing the Wada test, where one hemisphere of the brain is temporarily deactivated with sodium amytal Alema,...

The Effects of Anxiolytic Drugs

Gray and McNaughton were able to report a major success of the theory presented above, having to do with new anxiolytic drugs. In order to appreciate these findings, one must note that in addition to the effects of anxiolytic drugs on the 7.7-Hz dip in the theta-driving curve already described, McNaughton e.g., Coop, McNaughton, Warnock, amp Laverty, 1990 McNaughton amp Coop, 1991 McNaughton amp Sedgwick, 1978 later found a second universal effect. This research was in part a response to the...

Turhan Canli

Recent methodological advances in genetics and neuroscience have catalyzed work on the biological basis of personality and individual differences. Yet even active researchers rarely have the opportunity to learn about all of these developments, because geneticists, psychologists, and neuroscientists only rarely attend the same scientific meetings. This lack of communication motivated a remarkable conference that was held in August 2004 on the campus of Stony Brook University on Long Island, New...

Don C Fowles

To understand Jeffrey Gray's work, it is essential to understand the importance of 1 the anxiolytic drugs and 2 the theoretical framework provided by the tradition of animal learning theory, which had been a dominant force in psychology for much of the 20th century up to about the 1960s, when the cognitive revolution gained ascendancy. Gray reasoned that it ought to be possible to conceptualize the underlying processes by which the anxiolytic drugs exert their effects in terms of the constructs...