Self-stimulation Behavior Research Articles

Early experience as a determinant of adult behavioural responses to reward: the effects of repeated maternal separation in the rat

Depression is a major public health concern, representing one of the most significant causes of disability and morbidity. Despite significant advances in the definition of specific cognitive, emotional and neural dysfunctions that are associated with depression, there has been frustratingly little progress in the elucidation of plausible aetiological and pathophysiological mechanisms. The complex, multi-system dysfunctions of depressive illness do not lend themselves to hypothesis-driven, systematic manipulation in patients. For this reason, there is a need to develop valid and reliable models of affective psychopathology in laboratory animals. In this paper, we review briefly some of our previous work demonstrating that a specific periodic neonatal maternal separation procedure leads to a robust constellation of behavioural changes in the adult rat that resemble core aspects of human depressive psychopathology. We also present data from a study of the adult effects of the same manipulation on electrical intracranial self-stimulation behaviour. These data further support the hypothesis that it is possible to model vulnerability to anhedonia in the adult rat by manipulation of early experience.

Indications for Microvascular Upper Extremity Reconstruction

This article defines the optimum choices for soft tissue and bone defects in upper extremity reconstructions. Under certain circumstances, pedicle flaps may be a better choice than microvascular tissue transfer. Some of the pedicle transfers such as the intrinsic hand flaps and pedicled vascularized bone grafts around the wrist require microvascular tissue handling techniques, although a microvascular anastomosis is not specifically performed. Although refinements in pedicle flaps have defined their role in reconstructive upper extremity surgery, many reconstructions could not be performed without microvascular tissue transfer. Specific indications for microvascular upper extremity reconstruction are discussed.

A clinical and neurobehavioural review of high-functioning autism and Asperger's disorder.

To compare, contrast and review clinical and neuropsychological studies of high-functioning autism and Asperger's disorder. This paper reviews past and contemporary conceptualizations of autism and Asperger's disorder, together with epidemiological information, genetic and neurobehavioural findings. This paper focuses on neurobehavioural studies, in particular, executive functioning, lateralization, visual-perceptual and motor processing, which have provided an important source of information about the potential neurobiological dissociation that may exist between autism and Asperger's disorder. The clinical profiles of autism and Asperger's disorder contain a mixture of psychiatric and neurological symptoms: for example, movement abnormalities (i.e. stereotyped behaviours, hand flapping, toe walking, whole-body movements), atypical processing of parts and wholes, verbal and non-verbal deficits, ritualistic/compulsive behaviour, disturbances in reciprocal social interaction and associated depression and anxiety. The considerable clinical overlap between autism and Asperger's disorder has led many to question whether Asperger's disorder is merely a mild form of autism, or whether it should be considered as a separate clinical entity. In light of the growing body of epidemiological information, genetic, and neurobehavioural evidence that distinguishes autism from Asperger's disorder, it is premature to rule out the possibility that these disorders may be clinically, and possibly neurobiologically separate.

Discussion of “Microtransfer for Nail and Fingertip Injuries”

The foot donor site scars and the scars on the recipient finger have discouraged all but the most driven from having microvascular free flaps of the distal toe moved to the hand. Lille et al [1] reported free nonvascularized composite toenail grafts in 10 patients, with two excellent, three good, two fair, and three poor results. Sellah et al [2] reported 11 good results in 14 patients with a similar technique. Although free vascularized toenail grafts have more consistent improvement they are less resource, time, and expense saving, as both authors point out in 2000. In the 1991 Hand Clinics [3] Morrison described the toe wrap around flap for nail replacement to the finger, which they had described originally in 1980 [4]. Since then, there has been an evolution of methods of nail transfer that reduces scarring. Wei et al [5] (1993) published the largest series of microvascular transfer (152) from toe to finger with a 98% success rate. Koshima et al [6] (1988) described two patients for which they transferred toenails to the hand. Woo and Seul [7] (1998) reported 25 cases of partial toenail transfers. They used a portion of the toenail only, which resulted in a small nail when other than the large toe was used. Shibata et al [8] (1991) reported 10 patients in whom nails were transferred on a long pedicle anastomosed to digital vessels in the distal hand. Significant scars resulted, especially on the foot. Nakayama et al [9] (1990) described using a two-vein pedicle of the perionychium, one anastomosed to a digital artery and the other to a digital vein of the finger in three patients. The results were good, with less foot scars. Endo et al [10] reported the short pedicle vascularized nail flap with scars more distal and less extensive on the finger and toe in 1996. Dautel et al [11] (1998) also used a short vascular pedicle to decrease scarring. The ‘‘Evolution of Nail Transfer’’ by Endo et al [12] (1997) suggests using bone grafts from the iliac crest for bone replacement. What will be the longterm future of free nonvascularized grafts? Will they persist or resorb? Foucher et al [13] (1991) and Koshima et al, in 1992 [14], 1993 [15], and 2000 [16], described use of the pad, distal phalanx, and nail to replace distal amputations and correct hooked nails. The bone supports the tip and nail bed without the problem of resorption of a free nonvascularized bone graft. Hirase et al [17] (1997) reported 60 free innervated finger flaps in the hand and osteo-onychocutaneous flaps from the toe. Hopefully, the next generation of microsurgeons will continue to make fewer and better scars with improved results.

Exposure to chronic mild stress alters thresholds for lateral hypothalamic stimulation reward and subsequent responsiveness to amphetamine

Chronic mild stress in rodents has been proposed to model some of the environmental factors that contribute to the induction of depressive disorders in humans. This model is based on the hypothesis that chronic mild stress induces a change in brain reward function that resembles the symptomatology of major depression, namely, a decrease in responsiveness to rewarding stimuli. The purpose of the first experiment was to investigate whether chronic mild stress affects brain reward function as measured by alterations in lateral hypothalamic self-stimulation behavior in rats. Exposure to chronic mild stress induces a reduction in body weight which might affect brain reward function on its own. Therefore, the potential contribution of a reduction in body weight to the chronic mild stress-induced alterations in brain reward function was examined in a separate group of food-restricted rats. Thresholds for lateral hypothalamic self-stimulation were slightly but significantly lowered in animals exposed to chronic mild stress, indicating an enhancement of stimulation reward efficacy. Food restriction had no effect on brain reward function. The second experiment examined the interaction between prior exposure to chronic mild stress or food restriction and responsiveness to a pharmacological challenge, amphetamine, that enhances brain reward function. Acute administration of amphetamine produced a greater enhancement of lateral hypothalamic self-stimulation reward in animals exposed to chronic stress relative to non-stressed and food-restricted animals. Taken together, the present findings indicate that chronic mild stress sensitizes the neural substrates that mediate both lateral hypothalamic stimulation and psychostimulant drug reward. These findings support the hypothesis that prior exposure to stress affects the vulnerability for drug-taking behavior by increasing the positive reinforcing properties of drug of abuse.

Motility disorders in childhood: Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.

Motility disorders in childhood: Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.

Use of a GABA-transaminase agonist for treatment of infantile autism

This paper describes the use of a GABA-transaminase agonist for the treatment of infantile autism. An approximate one third reduction of GABA and ammonia levels for an autistic patient with noticeable improvement of verbal/language skills and a reduction of repetitious ritualistic self-stimulatory behavior (stimming) was observed. A reduction of the plasma GABA (by administrating a GABA-T agonist, Imipramine) probably results in more axon(s)-to-oligodendrocyte signaling in the corpus callosum and it is postulated that this could result in a reduction of the autistic features for the patient.

Evaluation and treatment of covert stereotypy

AbstractThe treatment of behavior maintained by automatic reinforcement (e.g. stereotypy) can present a unique challenge if practitioners cannot control delivery of the maintaining reinforcer. Further, some individuals might engage in stereotypy only when care providers are absent. In the current evaluation, an adolescent boy's hand flapping was demonstrated to occur in the absence of social contingencies and care providers. To reduce the behavior, two treatment strategies were assessed. In the first approach, verbal reminders to refrain from hand flapping were delivered on time‐based schedules. In the second approach (differential reinforcement of other behavior, DRO), we provided access to a preferred item contingent on prespecified time lengths with no hand flapping when the participant was alone in a room. Results of the investigation indicated that the verbal reminders were unsuccessful, whereas the DRO program resulted in near‐zero levels of stereotypy. Copyright © 2002 John Wiley & Sons, Ltd.

Behavior therapy and autism: Issues in diagnosis and treatment.

Behavior analysis has demonstrated utility when it comes to the treatment of autism. Still behavior analysts continue to refine and develop their techniques. This article conceptualizes autism within a behavior analytic model of child development and characterizes several promising techniques for increasing language use and spontaneity. These areas are detailed sufficiently to inspire new research and aid consultants in designing interventions and a more comprehensive curriculum for children with autism. ********** For behavior therapists and specialists, developmental psychopathology is an area of growing interest. Developmental psychology is the field of psychology-concerned changes in the individual across the life span. To accomplish this task, this approach attempts to observe children/adults over extended periods. Psychopathology is the area of psychology that studies clusters of behaviors that predict decreases in life satisfaction or ability to function. Together these two areas combine to study and predict long term outcomes for a child with behavioral patterns considered problematic (Rutter, 1994). One clusters of behavior patterns receiving particular attention by behavior specialists and therapists is children with autism. This article attempts to provide a review of state of the art treatment of autism for those working in the field. Autism comes from Greek, meaning stereotypy. The term autism was first used by Bleuler to describe a patient who withdrew socially from his environment (Kanner, 1971a). Several case studies of this syndrome were identified between Bleuler and Kanner. In 1943, Kanner applied the label of autism to eleven children who were socially aloof and self-isolated from a very early age. He studied these children extensively from early childhood through adulthood. After his study, he presented a detailed account of the children's adjustment and placement (Kanner, 1971b). He described the prognosis for this disorder as poor. In Kanner's view, infantile autism was distinctly different from mental retardation, other disorders and childhood schizophrenia. Since children with retardation are generally responsive to adults, Kanner used the lack of social responsiveness to support the conditions as distinct disorders. With conditions like schizophrenia, the child would obtain a normal level of functioning and then would have withdrawn from that level. In contrast autism is a syndrome where the child has never functioned at an adequate level. Also, having autism does not place the child at a greater risk of developing schizophrenia then the general population (Volkmar & Cohen, 1991). Also, in general children with autism have poorer social skills and show marked deficits in language (Matese, Matson, & Sevin, 1994). This suggests that these disorders may have different origins (Margolies, 1977). The most defining feature of autism, according to Kanner (1943), was the child's inability to relate to other children and adults. Under this umbrella, he defined the following characteristics: disruption in language development; or a complete failure to develop language; a need to maintain a constant environment (no changes); monotonous repetitions of behavioral sequences such as hand flapping or twirling; good intellectual abilities in very restricted areas; and little spontaneous play activities. Current Issues in the DSM-IV Diagnosis The patterns of behavior diagnosed as autism occurs in 4.5 out of 10,000 children. Although Kanner believed autistic children were of average intelligence, this is most often not true (Rutter, 1983). Consistently, empirical investigations reveal approximately 80 percent of children with autism score below 70 (1) on standardized intelligence tests, placing them within the range of mental retardation (Ghaziuddin, Tsai, & Ghaziuddin, 1992; Rutter, 1983). Since the scores for the two groups (mental retardation and autism) are similar, sometimes they are hard to differentiate (Kamphaus & Frick, 1996). …

GABA-transaminase, the liver and infantile autism

Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter of the mammalian brain and the enzyme responsible for catabolism (breakdown in the liver during regulation) is GABA-Transaminase (GABA-T). Recently, Cohen (1) has shown that extremely high GABA levels in the urine and blood were observed for an autistic child. The finding that elevated levels of GABA in the urine and blood are present for an autistic child could explain why autistic features (such as self-stimulatory behavior and language delays, etc.) are found. Increasing the GABA-T enzyme activity for this autistic patient could result in less plasma GABA (after liver regulation) entering into the bloodsteam and brain and it is postulated that this could result in a reduction of the autistic features (such as self-stimulatory behavior and language delays, etc.) due to abnormal development of the axon(s) in the corpus callosum.

Effects of a weighted vest on attention to task and self-stimulatory behaviors in preschoolers with pervasive developmental disorders.

This study examined the effectiveness of using a weighted vest for increasing attention to a fine motor task and decreasing self-stimulatory behaviors in preschool children with pervasive developmental disorders (PDD). Using an ABA single-subject design, the duration of attention to task and self-stimulatory behaviors and the number of distractions were measured in five preschool children with PDD over a period of 6 weeks. During the intervention phase, all participants displayed a decrease in the number of distractions and an increase in the duration of focused attention while wearing the weighted vest. All but 1 participant demonstrated a decrease in the duration of self-stimulatory behaviors while wearing a weighted vest; however, the type of self-stimulatory behaviors changed and became less self-abusive for this child while she wore the vest. During the intervention withdrawal phase, 3 participants experienced an increase in the duration of self-stimulatory behaviors, and all participants experienced an increase in the number of distractions and a decrease in the duration of focused attention. The increase or decrease, however, never returned to baseline levels for these behaviors. The findings suggest that for these 5 children with PDD, the use of a weighted vest resulted in an increase in attention to task and decrease in self-stimulatory behaviors. The most consistent improvement observed was the decreased number of distractions. Additional research is necessary to build consensus about the effectiveness of wearing a weighted vest to increase attention to task and decrease self-stimulatory behaviors for children with PDD.

Effects of the cannabinoid receptor agonist CP 55,940 and the cannabinoid receptor antagonist SR 141716 on intracranial self-stimulation in Lewis rats

Lewis rats were trained to self-stimulate the medial forebrain bundle (MFB) using a rate-frequency paradigm. They were then tested for the effects of the cannabinoid receptor agonist CP 55,940, the selective cannabinoid receptor antagonist SR 141716 and the dopamine D 1 receptor antagonist SCH 23390. CP 55,940 (0, 10, 25 and 50 μg/kg i.p.) had no effect on MFB self-stimulation behaviour as assessed by the M 50, the stimulation frequency at which half-maximal response rates were obtained. With SR 141716, only a very high dose (20 mg/kg i.p.) caused a significant inhibition of the rewarding efficacy of the stimulation. This was seen as an increase in the M 50. All other doses of SR 141716 (0, 1, 3, 10 mg/kg i.p.) were ineffective in modulating the M 50. By comparison, a relatively low dose (0.06 mg/kg i.p.) of SCH 23390 caused a large increase in M 50. These results indicate a relatively modest influence, if any at all, of exogenous or endogenous cannabinoids on reward-relevant neurotransmission.

Neuroprotective and behavioral effects of the selective metabotropic glutamate mGlu 1 receptor antagonist BAY 36-7620

This study characterized the neuroprotective and behavioral effects of (3a S,6a S)-6a-naphtalen-2-ylmethyl-5-methyliden-hexahydro-cyclopenta[c]furan-1-on (BAY 36-7620), a novel, selective and systemically active metabotropic glutamate (mGlu) 1 receptor antagonist. In the rat, neuroprotective effects were obtained in the acute subdural hematoma model (efficacy of 40–50% at 0.01 and 0.03 mg/kg/h, i.v. infusion during the 4 h following surgery); whereas in the middle cerebral artery occlusion model, a trend for a neuroprotective effect was obtained after triple i.v. bolus application of 0.03–3 mg/kg, given immediately, 2 and 4 h after occlusion. Hypothermic effects were mild and only obtained at doses which were considerably higher than those at which maximal neuroprotective efficacy was obtained, indicating that the neuroprotective effects are not a consequence of hypothermia. BAY 36-7620 protected against pentylenetetrazole-induced convulsions in the mouse (MED: 10 mg/kg, i.v.). As assessed in rats, BAY 36-7620 was devoid of the typical side-effects of the ionotropic glutamate (iGlu) receptor antagonists phencyclidine and (+)-5-methyl-10,11-dihydroxy-5 H-dibenzo(a,d)cyclohepten-5,10-imine (MK-801). Thus, BAY 36-7620 did not disrupt sensorimotor gating, induce phencyclidine-like discriminative effects or stereotypical behavior, or facilitate intracranial self-stimulation behavior. Although behavioral stereotypies and disruption of sensorimotor gating induced by amphetamine or apomorphine were not affected by BAY 36-7620, the compound attenuated some behavioral effects of iGlu receptor antagonists, such as excessive grooming or licking, and their facilitation of intracranial self-stimulation behavior. It is concluded that mGlu 1 receptor antagonism results in neuroprotective and anticonvulsive effects in the absence of the typical side-effects resulting from antagonism of iGlu receptors.

Both GABA B receptor agonist and antagonists decreased brain stimulation reward in the rat

The present experiments were designed to determine the role of GABA B receptor function on brain stimulation reward. Using a discrete-trial current-intensity threshold procedure, dose-effect functions were generated for the GABA B receptor agonist CGP 44532 (0–1.0 mg/kg, s.c.) and the GABA B receptor antagonists CGP 56433A (0–10.0 mg/kg, s.c.) and CGP 51176 (0–300.0 mg/kg, s.c.) on brain reward thresholds in rats. The GABA B receptor antagonists CGP 56433A and CGP 51176 were used also to examine interaction effects with the GABA B receptor agonist CGP 44532 on reward thresholds. Administration of the highest doses of both the GABA B receptor agonist and antagonists elevated reward thresholds. Thus, both the agonist and antagonists used induced a reward decrement when administered separately. In addition, the co-administration of either of the two receptor antagonists with the agonist induced an additive effect on thresholds, rather than blocking the agonist-induced threshold elevations. These results suggest that activation of GABA B receptors modulates intracranial self-stimulation behavior in a complex fashion, possibly through differential effects of GABA B agonists and antagonists on pre- and post-synaptic GABA B receptors.

Local hand flaps

Wounds of the hand continue to be a challenge for the hand surgeon. The repair of hand wounds has evolved from the simple, such as allowing primary closure, to the complex, such as free tissue transfer. This evolution has occurred because of better understanding of the vascular supply to the skin of the hand along with the development of improved, more sophisticated surgical technique. Our review of the literature has shown numerous local hand flaps that have stood the test of time. Though lower on the reconstructive ladder, these flaps continue to aid the hand surgeon in dealing with soft tissue losses of the hand. It would be impossible to catalogue all local hand flaps in this article. Thus, we present many of the most useful and historic flaps, which we feel should be a part of every hand surgeon's armamentarium. Copyright © 2001 by the American Society for Surgery of the Hand

Use of distally based intermetacarpal flaps to cover dorsal traumatic defects of the middle fingers

The presence of distal intermetacarpal anastomoses between dorsal and palmar vascular networks makes it possible to dissect and isolate Distally Based Dorsal Hand (DBDH) flaps. Quaba and Davidson first described this possibility. The purpose of this paper is to report our experience using the DBDH flap to reconstruct complicated defects of the long fingers. We are reporting our experience in eight cases (seven performed in emergency) where such a flap was used to cover dorsal traumatic skin defects of the long fingers. The average age was 40.3 years, ranging from 25 to 67 years. All the patients were males, seven of them had a job at the time of injury and the last one had already retired when injured. All the eight flaps survived, sometimes with minor complications. Only one case developed a whole-thickness distal necrosis treated successfully by regular dressings. In one case, a Z-plasty was performed to correct a retraction in the 2nd web-space two months after surgery. Many flaps have been described to cover dorsal skin defects in the fingers. All of them display some advantages and some disadvantages. The use of this flap allows coverage of vast skin defects and thereby early finger mobilisation. The surgical technique is rather easy, and it does not require microsurgical experience. Skin grafting to cover donor site is not always necessary.

Validation of stress-induced anhedonia and ventral tegmental self-stimulation behavior in the rat

Validation of stress-induced anhedonia and ventral tegmental self-stimulation behavior in the rat

Parametric Analysis of Overcorrection Duration Effects

Positive practice overcorrection (PPOC) has long played a significant role in the behavioral treatment of serious self-stimulatory behavior. Three experiments comparing the effectiveness of 30-second, 2-minute, and 8-minute PPOC on reduction of stereotypic hand behavior of adults with severe to profound developmental disabilities were conducted to resolve inconsistencies in previously reported findings concerning the role of PPOC duration in response suppression. Experiment 1, which used an alternating treatments--multiple baseline design, suggested that the different durations were equally effective in reducing the stereotypic behaviors to near-zero levels. Experiment 2, which used a reversal design, supported the findings of Experiment 1. Experiment 3, which used a reversal design to test the shortest and longest durations, generally confirmed the results of the first two experiments. This study therefore failed to support the oft-claimed superiority of long-duration PPOC. The possible factors underlying these findings and their implications for future research and practice are discussed.

Differential sensitivity of the caudal and rostral nucleus accumbens to the rewarding effects of a H1-histaminergic receptor blocker as measured with place-preference and self-stimulation behavior

A recent series of studies in rats has demonstrated positively reinforcing and memory enhancing effects following lesions of the nucleus tuberomammillaris, which is the only known source of neuronal histamine. The aim of the present experiments was to assess whether inhibition of histaminergic neurotransmission in the ventral striatum has positively reinforcing effects. In Experiment 1 rats with chronically-implanted cannulae were injected with the H1 receptor blocker d-(+)-chlorpheniramine at doses of 0.1, 1.0 and 10.0 μg into the rostral or caudal parts of the nucleus accumbens, a brain region known to be involved in reward-related processes. Immediately after the treatment the animals were placed into one of four restricted quadrants of a circular open field (closed corral) for a single conditioning trial. During the drug-free test for conditioned place preference, when a choice among the four quadrants was provided, those rats injected with 10.0 μg chlorpheniramine in the caudal nucleus accumbens spent more time in the treatment corral, indicative of a positively rewarding drug action. In Experiment 2 the question was posed whether injection of chlorpheniramine into the nucleus accumbens influences electrical self-stimulation of the lateral hypothalamus. For this purpose rats were chronically implanted with two bipolar electrodes aimed at the lateral-hypothalami and with two additional guide cannulae aimed either at the rostral or caudal nucleus accumbens. After having established reliable self-stimulation behavior at one of the two electrode sites the animals were allowed to self-stimulate for one hour (baseline). Then they were unilaterally injected with 10.0 μg chlorpheniramine or vehicle and allowed to self-stimulate for another hour (test). On the next day the same procedure took place, except for the difference that the animals received an injection aimed at the hemisphere not treated so far. Animals treated with chlorpheniramine in the caudal and in the rostral nucleus accumbens displayed higher rates of ipsihemispheric self-stimulation behavior. Moreover, the animals treated with the H1 receptor blocker in the caudal nucleus accumbens displayed higher rates of ipsihemispheric self-stimulation than those having received an injection in the rostral pole. Upon completion of this part of the experiment all animals received an additional intraperitoneal treatment with chlorpheniramine (20 mg/kg) or vehicle, respectively, and were tested in the same way described above. This treatment also resulted in an amplification of intracranial self-stimulation behavior. These results support the hypothesis that histaminergic neurotransmission is involved in the inhibitory control of a central system subserving reward-related processes. The present data also further highlight the nucleus accumbens as functionally heterogenous along its rostrocaudal axis, with the caudal-shell subregion being more sensitive to antihistaminic induced reward than the rostral entity.

Differential effects of withdrawal from chronic amphetamine or fluoxetine administration on brain stimulation reward in the rat--interactions between the two drugs.

Withdrawal from chronic amphetamine administration is characterized by deficits in reward that resemble some symptoms of depression. Nevertheless, the effects of long-term administration and withdrawal from other drugs, such as fluoxetine, that have the potential to elevate mood in depressed individuals have not been characterized. The purpose of this study was to characterize the effects of withdrawal from chronic amphetamine or fluoxetine administration on central reward function. Furthermore, the effects of acute or chronic pretreatment with fluoxetine on responsiveness to an acute amphetamine challenge were examined to identify potential interactions between the two drugs. A rate-independent discrete-trial threshold procedure was used to characterize self-stimulation behavior in rats prepared with bipolar electrodes in the medial forebrain bundle. Elevations in intracranial self-stimulation (ICSS) thresholds, reflecting a decrease in the reward value of the stimulation, were associated with withdrawal from various chronic amphetamine treatment regimens (1-5 mg/kg, three injections per day for 1, 2, 4 or 6 days). The magnitude and duration of threshold elevations were proportional to the duration and dose of amphetamine treatment prior to withdrawal. In contrast, no alterations in ICSS thresholds were associated with withdrawal from chronic fluoxetine treatment (5 mg/kg/day for 15 days). While neither acute nor chronic administration of fluoxetine alone altered ICSS thresholds, chronic pretreatment with fluoxetine blocked the threshold-lowering effect of acute amphetamine administration (4 mg/kg), but acute pretreatment did not. Amphetamine-induced decreases in response latency, a measure of motor performance, were not affected by either chronic or acute fluoxetine pretreatment. The results of these experiments suggest that chronic fluoxetine treatment may induce adaptive changes in serotonergic transmission that, in themselves, do not alter the function of central reward processes, but may alter the ability of amphetamine to potentiate ICSS reward. In addition, the lack of change in ICSS thresholds during withdrawal from the chronic fluoxetine treatment regimen used suggests that withdrawal from all mood-altering drugs may not necessarily produce changes in central reward functions.