Targeting dynorphin/kappa opioid receptor systems to treat alcohol abuse and dependence

This review represents the focus of a symposium that was presented at the “Alcoholism and Stress: A Framework for Future Treatment Strategies” conference in Volterra, Italy on May 3–6, 2011 and organized/chaired by Dr. Brendan M. Walker. The primary goal of the symposium was to evaluate and disseminate contemporary findings regarding the emerging role of kappa-opioid receptors (KORs) and their endogenous ligands dynorphins (DYNs) in the regulation of escalated alcohol consumption, negative affect and cognitive dysfunction associated with alcohol dependence, as well as DYN/KOR mediation of the effects of chronic stress on alcohol reward and seeking behaviors. Dr. Glenn Valdez described a role for KORs in the anxiogenic effects of alcohol withdrawal. Dr. Jay McLaughlin focused on the role of KORs in repeated stress-induced potentiation of alcohol reward and increased alcohol consumption. Dr. Brendan Walker presented data characterizing the effects of KOR antagonism within the extended amygdala on withdrawal-induced escalation of alcohol self-administration in dependent animals. Dr. Georgy Bakalkin concluded with data indicative of altered DYNs and KORs in the prefrontal cortex of alcohol dependent humans that could underlie diminished cognitive performance. Collectively, the data presented within this symposium identified the multifaceted contribution of KORs to the characteristics of acute and chronic alcohol-induced behavioral dysregulation and provided a foundation for the development of pharmacotherapeutic strategies to treat certain aspects of alcohol use disorders.     

Neurobiological mechanisms contributing to alcohol-stress-anxiety interactions

This article summarizes the proceedings of a symposium that was presented at a conference entitled “Alcoholism and Stress: A Framework for Future Treatment Strategies.” The conference was held in Volterra, Italy on May 6-9, 2008 and this symposium was chaired by Jeff L. Weiner. The overall goal of this session was to review recent findings that may shed new light on the neurobiological mechanisms that underlie the complex relationships between stress, anxiety, and alcoholism. Dr. Danny Winder described a novel interaction between D1 receptor activation and the corticotrophin-releasing factor (CRF) system that leads to an increase in glutamatergic synaptic transmission in the bed nucleus of the stria terminalis. Dr. Marisa Roberto presented recent data describing how protein kinase C epsilon, ethanol, and CRF interact to alter GABAergic inhibition in the central nucleus of the amygdala. Dr. Jeff Weiner presented recent advances in our understanding of inhibitory circuitry within the basolateral amygdala (BLA) and how acute ethanol exposure enhances GABAergic inhibition in these pathways. Finally, Dr. Brian McCool discussed recent findings on complementary glutamatergic and GABAergic adaptations to chronic ethanol exposure and withdrawal in the BLA. Collectively, these investigators have identified novel mechanisms through which neurotransmitter and neuropeptide systems interact to modulate synaptic activity in stress and anxiety circuits. Their studies have also begun to describe how acute and chronic ethanol exposure influence excitatory and inhibitory synaptic communication in these pathways. These findings point toward a number of novel neurobiological targets that may prove useful for the development of more effective treatment strategies for alcohol use disorders.     

Proceedings of the 2009 annual meeting of the Fetal Alcohol Spectrum Disorders Study Group

The annual meeting of the Fetal Alcohol Spectrum Disorders Study Group (FASDSG) was held on June 20, 2009 in San Diego, CA, as a satellite of the Research Society on Alcoholism Meeting. The FASDSG membership includes clinical, basic, and social scientists who meet to discuss recent advances and issues in Fetal Alcohol Spectrum Disorders research. The main theme of the meeting was “Epigenetics and Development.” Two keynote speakers, Dr. Randy Jirtle and Dr. Michael Skinner, addressed the role of epigenetics and environmental inputs, including alcohol, during critical stages of development and their potential critical and long-lasting effects. Members of the FASDSG provided new findings through brief “FASt” data reports, and national agency representatives provided updates on activities and funding priorities. Scientific presentations were made by recipients of the Student Research Merit Award and Rosett Award.     

Stress-related neuropeptides and alcoholism: CRH, NPY, and beyond

This article summarizes the proceedings of a symposium held at the conference on “Alcoholism and Stress: A Framework for Future Treatment Strategies” in Volterra, Italy, May 6-9, 2008. Chaired by Markus Heilig and Roberto Ciccocioppo, this symposium offered a forum for the presentation of recent data linking neuropetidergic neurotransmission to the regulation of different alcohol-related behaviors in animals and in humans. Dr. Donald Gehlert described the development of a new corticotrophin-releasing factor receptor 1 antagonist and showed its efficacy in reducing alcohol consumption and stress-induced relapse in different animal models of alcohol abuse. Dr. Andrey Ryabinin reviewed recent findings in his laboratory, indicating a role of the urocortin 1 receptor system in the regulation of alcohol intake. Dr. Annika Thorsell showed data supporting the significance of the neuropeptide Y receptor system in the modulation of behaviors associated with a history of ethanol intoxication. Dr. Roberto Ciccocioppo focused his presentation on the nociceptin/orphanin FQ (N/OFQ) receptors as treatment targets for alcoholism. Finally, Dr. Markus Heilig showed recent preclinical and clinical evidence suggesting that neurokinin 1 antagonism may represent a promising new treatment for alcoholism. Collectively, these investigators highlighted the significance of neuropeptidergic neurotransmission in the regulation of neurobiological mechanisms of alcohol addiction. Data also revealed the importance of these systems as treatment targets for the development of new medication for alcoholism.     

Habit formation: Implications for alcoholism research

Characteristics of individuals with severe alcohol use disorders include heightened cue sensitivity, compulsive seeking, craving, and continued alcohol use in the face of negative consequences. Animal models are useful for understanding behavioral and neurological mechanisms underlying problematic alcohol use. Seeking of operant reinforcers including alcohol is processed by two mechanisms, commonly referred to as “goal-directed” (action-outcome) and “habitual” (stimulus-response). As substance use disorders are characterized by continued use regardless of unfavorable outcomes, it is plausible that drug use causes an unnatural disruption of these mechanisms. We present a critical analysis of literature pertaining to behavioral neuroscience alcoholism research involving habit formation.     

The role of biogenic amine signaling in the bed nucleus of the stria terminals in alcohol abuse

There is a growing body of evidence that suggests that stress and anxiety can influence the development of alcohol use disorders. This influence is believed to be due in part to persistent adaptations in discrete brain regions that underlie stress responsivity. One structure that has been proposed to be a site of important neuroadaptations underlying this behavior is the extended amygdala. The extended amygdala is a series of extensively inter-connected limbic structures including the central nucleus of the amygdala (CeA) and the bed nucleus of the stria terminalis (BNST). These structures are critical regulators of behavioral and physiological activation associated with anxiety. Additionally, numerous reports have suggested that these regions are involved in increased drinking behavior associated with chronic alcohol exposure and withdrawal. The focus of this review will be to discuss the role of the BNST in regulation of behavior, to provide some insight in to the circuitry of the BNST, and to discuss the actions of the biogenic amines, serotonin, dopamine and norepinephrine, in the BNST.     

Reducing effect of the Chinese medicinal herb, Salvia miltiorrhiza, on alcohol self-administration in Sardinian alcohol-preferring rats

The dried roots of Salvia miltiorrhiza are highly valued in Chinese folk medicine for use in the prevention and treatment of a series of ailments. Previous studies have demonstrated that administration of standardized extracts of S. miltiorrhiza selectively reduced excessive alcohol drinking and relapse-like drinking in selectively bred Sardinian alcohol-preferring (sP) rats. The present study was designed to extend these findings on the “anti-alcohol” properties of S. miltiorrhiza extracts to operant procedures of oral alcohol self-administration. Two independent groups of sP rats were trained to lever-respond on an FR4 schedule of reinforcement for alcohol (15%, v/v) or sucrose (1–3%, w/v) in daily 30 min sessions. Once responding had stabilized, rats were tested under the fixed ratio 4 (FR4) schedule of reinforcement (index of alcohol reinforcing properties) and the progressive ratio (PR) schedule of reinforcement (index of alcohol motivational properties). Treatment with S. miltiorrhiza extract (0, 50, 100, and 200 mg/kg, intragastrically [i.g.]) markedly reduced lever responding for alcohol, amount of self-administered alcohol, and breakpoint for alcohol (defined as the lowest response requirement not achieved in the PR experiment). No dose of S. miltiorrhiza extract altered any parameter of sucrose self-administration. These results a) demonstrate that treatment with S. miltiorrhiza extract selectively reduced the reinforcing and motivational properties of alcohol in sP rats and b) extend to operant procedures of alcohol self-administration previous data on the “anti-alcohol” effects of S. miltiorrhiza extracts. These data strengthen the notion that novel pharmacological approaches for treatment of alcohol use disorders may stem from natural substances.     

Urocortins: CRF's siblings and their potential role in anxiety,depression and alcohol drinking behavior

It is widely accepted that stress, anxiety, depression and alcohol abuse-related disorders are in large part controlled by corticotropin-releasing factor (CRF) receptors. However, evidence is accumulating that some of the actions on these receptors are mediated not by CRF, but by a family of related Urocortin (Ucn) peptides Ucn1, Ucn2 and Ucn3. The initial narrow focus on CRF as the potential main player acting on CRF receptors appears outdated. Instead it is suggested that CRF and the individual Ucns act in a complementary and brain region-specific fashion to regulate anxiety-related behaviors and alcohol consumption. This review, based on a symposium held in 2011 at the research meeting on “Alcoholism and Stress” in Volterra, Italy, highlights recent evidence for regulation of these behaviors by Ucns. In studies on stress and anxiety, the roles of Ucns, and in particular Ucn1, appear more visible in experiments analyzing adaptation to stressors rather than testing basal anxiety states. Based on these studies, we propose that the contribution of Ucn1 to regulating mood follows a U-like pattern with both high and low activity of Ucn1 contributing to high anxiety states. In studies on alcohol use disorders, the CRF system appears to regulate not only dependence-induced drinking, but also binge drinking and even basal consumption of alcohol. While dependence-induced and binge drinking rely on the actions of CRF on CRFR1 receptors, alcohol consumption in models of these behaviors is inhibited by actions of Ucns on CRFR2. In contrast, alcohol preference is positively influenced by actions of Ucn1, which is capable of acting on both CRFR1 and CRFR2. Because of complex distribution of Ucns in the nervous system, advances in this field will critically depend on development of new tools allowing site-specific analyses of the roles of Ucns and CRF.     

Alcohol-drinking patterns and metabolic syndrome risk: the 2007 Korean National Health and Nutrition Examination Survey

Alcohol consumption has been known to be related to the prevalence of metabolic syndrome (MS). Although some studies have revealed that mild to moderate alcohol consumption reduces the risk of MS, most of these studies have focused the effect of alcohol consumption amount on MS. We examined the association between alcohol-drinking patterns and MS by using the alcohol use disorders identification test (AUDIT) questionnaire to study 1,768 alcohol drinkers (847 men, 921 women) aged 20-75 years from Korean National Health and Nutrition Examination Survey in 2007. When compared with the subjects in the reference group (AUDIT score ≤7), the odds ratios (ORs, 95% confidence intervals [CIs]) for MS of subjects in the highest group (AUDIT score ≥16) were 3.92 (2.40-6.22) in men and 2.27 (0.87-5.89) in women after adjusting for confounding variables. Among the items of the AUDIT score, several alcohol-drinking patterns, including “drinking frequency,” “usual drinking quantity,” “frequency of high-risk drinking,” “frequency of inability to stop drinking,” “frequency of feeling guilty after drinking,” and “frequency of inability to remember after drinking” were strongly associated with the prevalence of MS in men. In women, there were significant relationships between MS and “usual drinking quantity,” “frequency of feeling guilty after drinking,” and “frequency of inability to stop drinking.” In summary, AUDIT score was strongly associated with MS in Korean adults, particularly in men. Accordingly, in addition to the amount of daily alcohol consumption, alcohol-drinking patterns should be addressed in the prevention and treatment of MS.     

Treatment of alcoholism as a chronic disorder

Alcoholism is a common disorder that tends to be chronic and relapsing. Although there is clear evidence that treatment can be expected to induce a period of remission or at least decreased symptoms, treatment of alcoholism is generally regarded as unsuccessful. Alcoholism should be approached as a chronic medical disorder such as diabetes or arthritis. Complete abstinence is the preferred goal, but “cures” or permanent abstinence from alcohol are rare. In this model, treatment benefits may be measured by length of remission, reduction in alcohol use, improvement in health and enhancement of social functioning. Treatment continues over a period of years, mainly on an outpatient basis with increasing intensity if symptoms recur. Medications that reduce craving for alcohol or diminish the euphoric effects of alcohol would be very helpful in the management of this chronic disorder. Preclinical studies have produced evidence for involvement of the endogenous opioid system in the reinforcing effects of alcohol. Recent controlled clinical trials of the opiate receptor antagonist naltrexone suggest that medications of this type may improve the results of treatment for alcoholism.     

Moderate alcohol consumption enhances vaccine-induced responses in rhesus macaques

We have recently shown that chronic alcohol consumption in a rhesus macaque model of ethanol self-administration significantly modulates the serum cytokine profile. In this study, we extended these observations by investigating the impact of chronic ethanol exposure on the immune response to Modified Vaccinia Ankara (MVA). All animals were vaccinated with MVA before ethanol exposure to ethanol and then again after 7 months of 22 h/day of “open-access” drinking of 4% (w/v) ethanol. Our results indicate that animals whose blood ethanol concentration (BEC) chronically exceeded 80 mg/dl had lower CD4 and CD8 T cell proliferation as well as IgG responses following MVA booster than control animals. In contrast, relatively moderate drinkers whose BEC remained below 80 mg/ml exhibited more robust MVA-specific IgG and CD8 T cell responses than controls. To begin to uncover mechanisms underlying the differences in MVA-specific responses between the three groups, we analyzed plasma cytokine levels and microRNA expression in peripheral blood mononuclear cells following MVA booster. Our findings suggest that moderate ethanol consumption results in higher levels of antiviral cytokines and an expression profile of microRNAs linked to CD8 T cell differentiation. In summary, moderate alcohol consumption enhances recall vaccine responses, whereas chronic alcohol intoxication suppresses this response.     

The management of unacceptable bleeding patterns in etonogestrel-releasing contraceptive implant users

The aim of this guidance is to review the management of unacceptable vaginal bleeding patterns in etonogestrel (ENG)-releasing contraceptive implant users concentrating, where possible, on the evidence for pharmacological treatments and identifying a pragmatic approach where this is not possible.This article was developed in accordance with methodology used for producing Royal College of Obstetricians and Gynaecologists' Green Top Guidelines.The Cochrane Library (including the Cochrane Database of Systematic Reviews, DARE and EMBASE) and Medline (1966–2010) were searched using the relevant MeSH terms, including all subheadings, and this was combined with a keyword search. Search words included “progestogen only contraceptives,” “contraceptive implants,” “progestogen implants,” “etonogestrel implants,” “irregular bleeding,” “unpredictable bleeding,” “bleeding irregularity” and “bleeding pattern,” and the search was limited to humans and English language. Enquiries for relevant information were also made to the pharmaceutical industry and researchers for missing studies.Although this is not a systematic review, two of the authors (D.M., I.S.F.), qualitatively assessed those papers reporting quantitative results involving treatments given either to stop or prevent bleeding in ENG or levonorgestrel contraceptive implants users.     

Lymphocyte measures in treatment-naïve 13-15-year old adolescents with alcohol use disorders

Many adolescents have chronic exposure to hazardous levels of alcohol. This is likely to be a significant predictor of health outcomes, including those related to immunity. We assessed substance use and biochemical immunological parameters in heavy drinking adolescents (meeting DSM-IV criteria for alcohol dependence) and light/nondrinking control adolescents in Cape Town. Lifetime alcohol dose, measured in standard units of alcohol, was orders of magnitude higher in alcohol-dependent (AD) participants than controls. All adolescent AD had a “weekends-only” style of alcohol consumption. The AD group was chosen to represent relatively “pure” AD, with minimal other drug use and no psychiatric diagnoses. With these narrow parameters in place, we found that AD adolescents were lymphopenic compared with controls, with significantly lower mean numbers of absolute circulating CD3+, CD4+, and CD8+ T-lymphocytes. On conclusion, we found that adolescent AD individuals with excessive alcohol intake, in a weekend binge-drinking style but without comorbid drug or psychiatric disorders, may be at increased risk of lymphopenia. This alcohol misuse may increase infectious disease susceptibility (including TB and HIV) by reducing immune system capabilities. Complex interactions of alcohol with other documented high-risk activities may further compound health risks.     

Endogenous cannabinoids in amygdala and hippocampus in post-mortem brains of Cloninger type 1 and 2 alcoholics

Accumulating evidence continues to link certain aspects of the endogenous cannabinoid (EC) system with alcohol dependence, negative-reinforcement learning, and the modulation of stress responses. Specific alterations in brain regions that are related to stress and negative-reinforcement learning have been reported to exist in Cloninger type 1 and type 2 alcoholics. To study possible differences in profiles of EC systems between Cloninger type 1 (n = 9) and type 2 (n = 8) alcoholics and non-alcoholic control subjects (n = 10), we analyzed post-mortem amygdala and hippocampus brain samples for several ECs by quantitative liquid chromatography with triple quadrupole mass-spectrometric detection. A significant difference was found between these 3 groups in terms of EC profiles in the amygdala (p = 0.037). In particular, this difference was prominent for variations in docosahexaenoylethanolamide levels, which were significantly higher in type 1 alcoholics (p = 0.022) when compared to controls. There was also a large negative correlation between anandamide concentration and mGlu1/5 receptor density in the hippocampi of Cloninger type 1 alcoholics (R = −0.88, p = 0.002), which was not seen in Cloninger type 2 alcoholics or in controls. Although preliminary, and from relatively small diagnostic groups, these results suggest that the EC system profile may be altered in the hippocampus and amygdala of Cloninger type 1 alcoholics.     

Gender differences in negative mood states in secondary school students: health survey in Catalonia (Spain)

Objective

To determine the prevalence of negative mood states in adolescents according to gender, to analyze variability among schools, and to evaluate the associated factors.

Methods

A cross-sectional study with a cluster design was carried out. We administered the High-school students health survey to a sample of 9,340 students (aged 14-16 years) in the third and fourth year of Compulsory Secondary Education in Catalonia, Spain, during the 2005-6 academic year. The main outcome measure was evidence of a negative mood state. A multilevel logistic regression model stratified by gender was used to identify the factors associated with negative mood states and to determine variability among distinct schools.

Results

Approximately 19% of adolescents reported evidence of a negative mood state, with a higher prevalence in girls (25%). The most significant factors associated with negative mood states were “use of tranquilizers” and “having eating disorders” in girls and “not exercising” and “poor self-perception of health status” in boys. In both genders, variability was found among schools in the prevalence of negative mood states (girls: variance = 0.078; p <0.001; boys: variance = 0.079; p = 0.012).

Conclusions

The prevalence of negative mood states in adolescent boys and girls was high. Differences were observed between genders in the factors related to these health states. The variability observed in the prevalence of negative mood states among distinct schools could not be explained by the study variables. Our results emphasize the association between the use of tranquilizers and negative mood states.     

Proceedings of the 2008 annual meeting of the Fetal Alcohol Spectrum Disorders Study Group

The annual meeting of the Fetal Alcohol Spectrum Disorders Study Group (FASDSG) was held on June 28, 2008 in Washington DC, as a satellite to the Research Society on Alcoholism meeting. The FASDSG membership includes clinical, basic, and social scientists who meet to discuss recent advances and issues in FASD research. The main theme of the meeting was “Factors that Influence Brain and Behavioral Development: Implications for Prevention and Intervention.” Two keynote speakers, Dr. Stephen Suomi and Dr. Carl Keen addressed how early environment and nutrition may influence outcome after prenatal alcohol exposure. The final keynote speaker, Kathy Mitchell, addressed issues regarding the relationship between scientists and the families with children with FASD. Members of the FASDSG provided updates on new findings through brief (FASt) data reports and national agency representatives provided updates of activities and funding priorities. Presentations were also made by recipients of the Student Research Merit award and Rosett award.     

Chronic ethanol and withdrawal effects on kainate receptor-mediated excitatory neurotransmission in the rat basolateral amygdala

Withdrawal (WD) anxiety is a significant factor contributing to continued alcohol abuse in alcoholics. This anxiety is extensive, long-lasting, and develops well after the obvious physical symptoms of acute WD. The neurobiological mechanisms underlying this prolonged WD-induced anxiety are not well understood. The basolateral amygdala (BLA) is a major emotional center in the brain and regulates the expression of anxiety. New evidence suggests that increased glutamatergic function in the BLA may contribute to WD-related anxiety following chronic ethanol exposure. Recent evidence also suggests that kainate-type ionotropic glutamate receptors are inhibited by intoxicating concentrations of acute ethanol. This acute sensitivity suggests potential (KA-R) contributions by these receptors to the increased glutamatergic function seen during chronic exposure. Therefore, we examined the effect of chronic intermittent ethanol (CIE) and WD on KA-R-mediated synaptic transmission in the BLA of Sprague-Dawley rats. Our study showed that CIE, but not WD, increased synaptic responses mediated by KA-Rs. Interestingly, both CIE and WD occluded KA-R-mediated synaptic plasticity. Finally, we found that BLA field excitatory postsynaptic potential responses were increased during CIE and WD via a mechanism that is independent of glutamate release from presynaptic terminals. Taken together, these data suggest that KA-Rs might contribute to postsynaptic increases in glutamatergic synaptic transmission during CIE and that the mechanisms responsible for the expression of KA-R-dependent synaptic plasticity might be engaged by chronic ethanol exposure and WD.     

Intermittent access to beer promotes binge-like drinking in adolescent but not adult Wistar rats

Teenagers are more likely than adults to engage in binge drinking and could be more vulnerable to long-term brain changes following alcohol abuse. We investigated the possibility of excessive adolescent drinking in a rodent model in which beer (4.44% ethanol vol/vol) is presented to adult and adolescent male Wistar rats. Experiment 1 tracked ad libitum beer and water consumption in group-housed rats from postnatal day (PND) 28-96. Rats consumed an average of 7.8 g/kg/day of ethanol during adolescence (PND 34-55) and this gradually declined to a lower level of intake in adulthood (PND 56-93) of 3.9 g/kg/day. In Experiment 2, beer was made available to both adolescent (PND 29+) and adult (PND 57+) rats for 2 h each day in a custom-built “lickometer” apparatus over 75 days. Access to beer was provided either 1 day out of every 3 (“intermittent” groups) or every day (“daily” groups). Relative to body weight, adolescent rats consumed more beer than adult rats in these limited access sessions. Adolescents with intermittent access consumed more than adolescents with daily access, a “binge”-like effect that was not observed in adult groups and that disappeared in adulthood. After 3 months of daily or intermittent alcohol consumption, the preference for beer versus sucrose was assessed. Rats previously kept under an intermittent schedule displayed a higher preference for beer relative to 3% sucrose, but only when testing occurred after 2 days of abstinence. In Experiment 3, adolescent (PND 30-37) and adult (PND 58-65) rats were given 20-min access to beer and their blood alcohol concentrations (BACs) were assessed. Adolescent groups consumed more alcohol than adults and showed higher BACS that were typical of human “binge” drinking (>80 mg/dL). Despite this, the correlation between BAC and beer intake was similar in both age groups. Together these results show that the intermittent presentation of alcohol itself appears to have subtle long-lasting effects on the motivation to consume alcohol. The findings support the use of beer solutions in modeling binge-like patterns of human alcohol consumption in adolescent rats.     

Aprendizaje colaborativo en red: el caso del Laboratorio de Telemedicina

This article analyzes the possibility of using social networks for teaching and learning telemedicine. The Telemedicine Laboratory is presented as a case study that offers a learning model supported by the development of a social network in a higher education environment. We performed a qualitative research study through an anonymous survey and participant observation. The results show that the Telemedicine Laboratory allows the generation of new knowledge from a holistic approach to reality, through communication and information technology, supported by the development of a social network. The presence of “invited experts” in the teaching and learning process and the linking of this process to problematic situations that members can “recognize” and perceive as true for their domain increase motivation and constitute success factors in the learning and teaching process.     

Rangeland degradation in North China: Perceptions of pastoralists

Rangeland degradation, a worldwide problem, is serious in China, especially in the Northern provinces. To assess the pastoralists’ perceptions toward rangeland trend and degradation, a survey was conducted in Ningxia, North China. Data were collected from a total of 284 pastoralists in six Ningxia counties. Findings showed that the majority of respondents believe the rangelands in Ningxia have been degraded, although there are some disparities among the counties that illustrate differing severity of degradation. Findings also clarified that the pastoralists have more knowledge about the “technical” and “supportive” aspects of conditions, while remaining less aware of “economic” and “management” factors of this issue. Yet, a high disparity was revealed between pastoralists’ perceptions among the counties in this study. The correlation matrix showed that most of their perceptions do not act independently. Findings also showed that those pastoralists who believe that their rangeland trend is “improved” have broader management and social perceptions than those who believe their rangeland is “degraded”. Finally, correlation analysis showed that the management and social perceptions have a negative correlation with degradation severity. Based on the findings, recommendations for possible interventions through extension/educational programs to diminish rangeland degradation are made. The programs are suggested to be presented in three packages including “management”, “social”, and “economic” issues in rangeland degradation.