Jochen Wolffgramm

Bio: Jochen Wolffgramm is an academic researcher from Free University of Berlin. The author has contributed to research in topics: Social deprivation & Etonitazene. The author has an hindex of 13, co-authored 25 publications receiving 1057 citations.

Social behavior, dominance, and social deprivation of rats determine drug choice.

Abstract: Relationships between social deprivation, dominance, and voluntary intake of ethanol (ETOH) and diazepam (D) were studied in male adult Wistar rats. Social behavior was registered by tetradic encounters in the open field prior to the rats' drug experiences. Social deprivation was induced by individual housing (LI) and contact caging (C). Nondeprived rats were housed in groups of four individuals (G) each. Social deprivation facilitated ETOH intake: LI rats consumed 30% more ETOH than G. Increase of deprivation by change of housing condition additionally raised ETOH consumption. ETOH experiences did not affect subsequent D choice. However, rats with a high ETOH consumption also preferred D. Individual drug disposition correlated with social dominance (in G: to social activity). Even in individual isolation dominant rats took less drugs than subordinate ones, but these rats raised their ETOH consumption when the housing conditions were changed. After nine months of voluntary ETOH intake and subsequently nine months without access to ETOH the rats showed signs of "behavioral dependence." Compared to naive animals they took twice as much ETOH and even after adulterating ETOH by quinine a high preference was perpetuated. During this state modifying social factors were no longer effective.

Free choice ethanol intake of laboratory rats under different social conditions.

Abstract: To study the effects of different kinds of social deprivation on voluntary ethanol (ETOH) intake male Wistar rats were housed by (a) individual caging, (b) “contact” caging (partial social deprivation), and (c) group caging (four individuals per cage). In the latter condition the individuals were separated once a week from each other for 24 h. The rats simultaneously received water 5%, 10% and 20% ETOH for a period of 14 weeks. Additional control animals received water. Isolated individuals drank significantly more alcohol than group-housed or contact-caged rats. After a few days they preferred the 20% solution. Circadian measures revealed a discontinuous intake of high doses (> 0.5 g/kg/h) during short time periods. Contact-caged rats consumed much less ETOH, but both the preference for 20% ETOH and the circadian course of intake were similar to those occurring after isolation. ETOH intake of group-housed individuals was low. These individuals preferred the 5% solution and continuously consumed small ETOH doses. During the period of short-term isolation they drank even more ETOH than long-term isolated individuals. In contrast to the latter, the enhancement of intake decreased after some weeks. It is suggested that the differences between the housing groups not only reflect different degrees of isolation stress, but may also be explained by a contribution of different reinforcing or aversive psychotropic effects of ETOH. Reduction of isolation stress is probably most important in the situation of short term separation, whereas dose-dependent reinforcement via social stimulation or sedation may affect the drug taking behavior under the other social conditions.

Animal models of addiction : models for therapeutic strategies?

Abstract: When having a continuous free choice in their home cages between water and alcohol- or drug-containing drinking solutions, rats first develop a controlled consumption of the psychotropic compound and, after several months, lose their control over drug taking. After a long period of abstinence, they reveal an excessive, compulsive drug intake. Adulteration of the drug-containing solutions reduces the doses taken by controlled consumers, but not those of the excessive drinkers, they can therefore be regarded as addicted. These animals show a pre-intake motor restlessness that may be related to craving. In two studies with putative anti-craving agents (the dopamine D2 receptor agonist lisuride and the D2 receptor antagonist flupentixol) we treated alcohol-addicted and non-addicted rats and observed the effects on alcohol taking, alcohol seeking and brain neurotransmission. These two investigations paralleled clinical studies, in both cases the results could be predicted correctly (“pro-craving” effect of both pharmaceutics). Differences between “symptomatic” and possible “causal” therapies are discussed, approaches towards a causal therapy according to an "imprinting"-model of an addition are suggested.

An animal model of compulsive food-taking behaviour.

Abstract: The increase in the incidence of obesity and eating disorders has promoted research aimed at understanding the aetiology of abnormal eating behaviours. Apart from metabolic factors, obesity is caused by overeating. Clinical reports have led to the suggestion that some individuals may develop addictive-like behaviours when consuming palatable foods, and compulsive eating plays a similar dominant role in obesity as compulsive drug taking does in drug addiction. The progress made in the development of treatment strategies for obesity is limited, in part, because the physiological and neurological causes and consequences of compulsive eating behaviour are not clearly understood and cannot readily be studied in human subjects. We have developed experimental approaches that reflect the functioning of the components of eating control, including compulsive food taking in rats. Rats that are given free choice between standard chow and a palatable, chocolate-containing 'Cafeteria Diet' (CD) develop distinct signs of compulsive food taking that appear at an early stage. These include the inability to adapt intake behaviour in periods of limited or bitter-tasting CD access, continued food intake during resting phases and changes in fine structure of feeding (duration, distribution and recurrence of feeding bouts). The model will help examine the neurobiological underpinnings of compulsive food seeking and food taking and provides a possibility to study the effects of novel anti-obesity compounds on compulsive eating and other components of food-taking behaviour in detail. For future use of genetic models, the possibility of a transfer to a mouse was discussed.

Neural systems of reinforcement for drug addiction: from actions to habits to compulsion

Abstract: Drug addiction is increasingly viewed as the endpoint of a series of transitions from initial drug use--when a drug is voluntarily taken because it has reinforcing, often hedonic, effects--through loss of control over this behavior, such that it becomes habitual and ultimately compulsive. Here we discuss evidence that these transitions depend on interactions between pavlovian and instrumental learning processes. We hypothesize that the change from voluntary drug use to more habitual and compulsive drug use represents a transition at the neural level from prefrontal cortical to striatal control over drug seeking and drug taking behavior as well as a progression from ventral to more dorsal domains of the striatum, involving its dopaminergic innervation. These neural transitions may themselves depend on the neuroplasticity in both cortical and striatal structures that is induced by chronic self-administration of drugs.

The incentive sensitization theory of addiction: some current issues

Abstract: We present a brief overview of the incentive sensitization theory of addiction. This posits that addiction is caused primarily by drug-induced sensitization in the brain mesocorticolimbic systems that attribute incentive salience to reward-associated stimuli. If rendered hypersensitive, these systems cause pathological incentive motivation (‘wanting’) for drugs. We address some current questions including: what is the role of learning in incentive sensitization and addiction? Does incentive sensitization occur in human addicts? Is the development of addiction-like behaviour in animals associated with sensitization? What is the best way to model addiction symptoms using animal models? And, finally, what are the roles of affective pleasure or withdrawal in addiction?

How does stress increase risk of drug abuse and relapse

Abstract: Rationale: The notion that stress leads to drug abuse in vulnerable individuals and relapse in addicts is not new. Most major theories of addiction postulate that stress plays an important role in increasing drug use and relapse. Several animal studies and some human laboratory studies have shown that stress exposure enhances drug self-administration. Although clinical observations suggest that exposure to stress increases drug use, and are associated with craving and relapse in addicts, human research in this area is largely correlational and at times contradictory. Objective: Given the growing preclinical evidence that supports the key role of stress in substance abuse, careful examination of this research area in humans is warranted. This paper examines empirical evidence on how stress may increase the vulnerability to drug abuse, and explores whether chronic drug abuse alters the stress response and coping in addicts, thereby increasing the likelihood of drug seeking and relapse. Unanswered questions on the association between stress and substance abuse in humans are identified. Conclusion: Preclinical research has shown that stress, in addition to drug itself, plays a key role in perpetuating drug abuse and relapse. However, the mechanisms underlying this association in humans remain unclear. A greater understanding of how stress may perpetuate drug abuse will likely have a significant impact on both prevention and treatment development in the field of addiction.