Paul J. Kulkosky’s research while affiliated with Colorado State University Pueblo and other places

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Publications (66)


Effect of CCK-8 on intake of caffeine, ethanol, and water
  • Article

May 2013

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15 Reads

Bulletin of the Psychonomic Society

Paul J. Kulkosky

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W. Eric Holst

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Wendy G. Smith

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Max A. Dietze

Three groups of 10 water-deprived female rats received access to solutions of caffeine (0.5 mg/ml), ethanol (5% w/v), or water, after i.p. injection of the neuropeptide and hormone cholecystokinin octapeptide (CCK-8; 0.5-4.0 µg/kg). Behavioral displays associated with intake of these fluids were quantified with an instantaneous time-sampling observational technique. CCK-8 dose-dependently reduced intake of ethanol solution, but not intake of caffeine solution or water. Feeding behavior reliably (p Ã.05) decreased after caffeine consumption, and activity level increased. Chemically induced anorexias were specific to ingesta; CCK-8 did not affect caffeine or water intake, or caffeine-induced anorexia, but it did inhibit ethanol intake and associated feeding behavior.


Satiation of Alcohol Intake

January 2012

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26 Reads

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6 Citations

This chapter reviews recent work that attempts to apply the analysis of satiation for food to the satiation of alcohol intake. Experiments and those of others reviewed here demonstrate reliable inhibitory effects of CCK, BN, and naloxone on the intake of alcohol. The identification of excitatory and satiating effects of these peptides suggests an integrative neuropeptide control system for the regulation of alcohol intake, preference, and blood levels. Revealing apparently common peptide mechanisms, the application has been successful so far.


Neuropeptidergic Control of Ethanol Intake

September 2008

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7 Reads

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2 Citations

Toxin Reviews

Abstract Neural peptides found in brain and gut tissues modulate the intake of ethanol by animals and humans. Experiments show that injections of sulfated cholecystokinin octapeptide, tetradecapeptide bombesin, angiotensin, and the opioid receptor blockers, naloxone and naltrexone, potently reduce oral consumption of ethanol solutions. Vasoactive intestinal peptide, neuropeptide Y, and galanin increase ethanol intake, and increases in blood levels of the opioid peptide beta endorphin are associated with relapse in alcoholics. Specific neuropeptide receptor blockers increase ethanol intake and prevent injected cholecystokinin and bombesin from inhibiting ethanol intake. Recently, naltrexone (Revia®) has been approved by the FDA for wider clinical use in the treatment of alcoholism. These findings support the hypothesis of neuropeptidergic regulation of alcohol consumption and innovative therapies for alcoholism.


Interaction of TRH and CCK in the satiation of alcohol intake

August 2004

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14 Reads

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4 Citations

Physiology & Behavior

Thyrotropin-releasing hormone (TRH) and cholecystokinin octapeptide (CCK) are endogenous neuropeptides known to inhibit intake of alcohol. Although both peptides are released by alcohol consumption and are hypothesized to satiate alcohol intake, their interaction has not been examined. We deprived ad-lib-fed male (n=6) and female (n=4) Wistar rats of water for 23 h and then gave them 30 min access to 5% w/v ethanol, followed by 30 min access to water. After adaptation to this schedule, rats were randomly assigned to receive intraperitoneal injections of either saline+saline, CCK (4 microg/kg)+saline, saline+TRH (10 mg/kg) or CCK+TRH immediately before alcohol access. Analyses of variance revealed a significant (P<.05) effect of CCK, and a significant interaction of CCK and TRH in control of ethanol consumption. CCK reliably reduced alcohol intake, and TRH blocked this satiation effect of CCK, increasing intake by 88.8% and 34.6% in males and females, respectively. TRH increased water intake in females, and CCK blocked this effect of TRH. Results indicate an infra-dose-additive interaction of CCK and TRH in satiation of alcohol intake, which may reflect a natural, endogenous neuropeptide interaction in the regulation of caloric intake.


Reproductive toxicity of the psoralens

May 2003

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55 Reads

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37 Citations

Pediatric Pathology & Molecular Medicine

The psoralens are naturally occurring secondary metabolites in plants, including many fruits and vegetables. Health risks have been associated with handling or ingesting psoralen-containing plants, and with the use of synthetic psoralens in photochemotherapy of skin disorders. Our research has demonstrated that administration of the psoralens bergapten (5-methoxypsoralen) and xanthotoxin (8-methoxypsoralen) in the diet of female rats reduced birthrates, number of implantation sites, pups, corpora lutea, full and empty uterine weight, and circulating estrogen levels in a dose-dependent manner. Psoralens induced mRNAs of the liver enzymes CYP1A1 and UGT1A6, suggesting that enhanced metabolism of estrogens by psoralen treatment may explain the reproductive toxicity and the observed reduction of ovarian follicular function and ovulation. Rats also avoided repeated consumption of a flavored solution associated with psoralen administration. The findings indicate that the psoralens constitute a novel group of ovarian toxicants. Further examination of the safety of their use in photochemotherapy and diet is warranted.


Thyrotropin releasing hormone decreases alcohol intake and preference in rats

February 2000

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25 Reads

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7 Citations

Alcohol

Thyrotropin releasing hormone (TRH) has been reported to reduce stress- and deprivation-induced eating, hypothetically by induction of satiation. Early work demonstrated thyroid extracts reduced alcohol intake, and recent research shows a TRH analog specifically inhibits alcohol preference. We determined whether parenteral administration of TRH reduces alcohol consumption and choice in a manner consistent with a satiation effect. Water-restricted ad lib fed female and male rats (n = 12) were given access to 5% w/v ethanol 0 or 30 minutes after intraperitoneal (i.p.) injection of TRH. TRH (20-40 mg/kg) inhibited alcohol intake only if injected immediately before alcohol access. Inhibition of alcohol intake was reliably accompanied by increased production of fecal boli but not by reliably decreased food intake. Rats given a choice of 2% w/v ethanol and water decreased alcohol preference after TRH (20 mg/kg) but did not reduce total fluid intake. Results are partially consistent with the hypothesis of TRH as one of several functional elements in the integrative neuropeptide control of alcohol consumption via short-term satiation.


Neurofeedback in the Treatment of Addictive Disorders

December 1999

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157 Reads

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53 Citations

This chapter explains neurofeedback in the treatment of addictive disorders. It has long been clear that alcoholism is associated with poor synchrony and deficient alpha EEG activity. Further, alcoholics have been shown more likely to increase the amount of alpha activity after consumption of alcohol. Taken together, these findings suggest that those with a predisposition to alcoholism have deficient alpha activity and are especially vulnerable to alcohol's capacity to produce an electroencephalographically measurable reinforcing state of increased slow-wave activity. The chapter discusses alpha-theta neurofeedback therapy and neurofeedback for addiction and PTSD. The chapter presents a schematic of the therapeutic procedures employed in the Peniston and Kulkosky brain wave neurofeedback therapy (PKBNT) for alcoholism and PTSD. The first step before using the Peniston and Kulkosky therapy involves psychiatric assessments and collection of personal data. These data include chronological age (years), alcoholic and/or PTSD history (years), prior hospitalizations (number), social position (Hollingshead's two-factor index), and intelligence quotient (Shipley Institute scale).


A novel group of ovarian toxicants: The psoralens

February 1999

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26 Reads

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34 Citations

Journal of Biochemical and Molecular Toxicology

Moussa M. Diawara

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K J Chavez

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[...]

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M R Franklin

The psoralens are naturally occurring metabolites found in many crop plants; synthetic forms of 5-methoxypsoralen (bergapten) and 8-methoxypsoralen (xanthotoxin) are widely used in skin photochemotherapy. Our previous research documented that dietary bergapten and xanthotoxin reduced birthrates in female rats when males and females were exposed to these chemicals. The present study was designed to determine the cause of this reduced birthrate and whether this resulted from direct impact on the females. The study demonstrates that bergapten and xanthotoxin administered, either alone or in combination to female rats (mated to undosed males), significantly reduced the number of implantation sites, pups, and corpora lutea in dosed females compared with control animals. Additionally, full uterine weight and empty uterine weight were significantly reduced. These compounds also significantly reduced circulating estrogen levels in a dose-dependent manner. Interestingly, the psoralens significantly induced mRNAs of liver enzymes typically induced by polycyclic aromatic hydrocarbons, CYP1A1 and UGT1A6; the higher the dose, the greater the induction. UGT 2B1 mRNA, typically induced by phenobarbital-like compounds, was not significantly affected. Thus, enhanced oxidative metabolism and conjugation of estrogens in psoralen-treated animals may provide a partial explanation for the effects observed. These findings are also consistent with psoralen-induced reduction in ovarian follicular function and ovulation.


Interaction of CCK and 8-OH-DPAT in the satiation of alcohol intake

December 1998

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10 Reads

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5 Citations

Alcohol

Administration of the neuropeptide cholecystokinin (CCK) is known to reduce food and alcohol intake and preference. The food satiation effect of CCK is reportedly dependent on serotonergic neurotransmission. Administration of 8-OH-DPAT, a serotonin1A autoreceptor agonist, reduces the ability of CCK to inhibit feeding. We determined if CCK's alcohol satiation effect also depends on activity of serotonergic neurons by administering 8-OH-DPAT (120-240 microg/kg) to 23-h water-deprived female and male rats, followed 1 h later by i.p. injection of CCK (4 microg/kg) and 30-min access to 5% w/v ethanol. 8-OH-DPAT significantly (p < 0.05) interacted with CCK, and reduced CCK's ethanol satiation effect when given i.p. but increased CCK's effect when given s.c. Female rats showed this interaction of 8-OH-DPAT with CCK at a higher dose than males when given i.p., but females were more sensitive to s.c. 8-OH-DPAT's ability to reduce ethanol intake. Results are consistent with previous findings of dose-, sex-, and route-dependent biphasic effects of 8-OH-DPAT on feeding and ethanol intake. A partial dependence of CCK's alcohol satiation effect on serotonergic neurotransmission is revealed in this design.


Mammalian toxicity of 5-methoxypsoralen and 8-methoxypsoralen, two compounds used in skin photochemotherapy

June 1997

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6 Reads

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11 Citations

Journal of Natural Toxins

The linear furanocoumarins (or psoralens) are plant secondary metabolites found in many plant groups, including common grocery fruits and vegetables. The psoralens have been used since ancient times in skin photochemotherapy; however, their medicinal use has been associated with skin cancer and other health hazards in humans. These compounds have been reported to be carcinogenic, mutagenic, teratogenic, and to cause phytophotodermatitis (an epidermal reaction symptomized by bullous eruptions, pigmentation, and potential vesicle formation). We examined the potential for 5-methoxypsoralen (bergapten) and 8-methoxypsoralen (xanthotoxin or methoxsalen)-dependent toxicity in tissues other than skin when administered by diet. Increasing concentrations (0, 250, 1250, and 2500 ppm) of each of the two chemicals were mixed into the powdered diet of male and female outbred Wistar rats. We observed for the first time that ingestion of bergapten and/or xanthotoxin decreased weight gain and birthrate of rats. Both of these parameters significantly decreased as the dietary concentrations of each of the two furanocoumarins increased. Combining the two chemicals at 1,250 ppm each resulted in a greater growth inhibition than when individual chemicals were added alone to the diet at 2,500 ppm. All psoralen-containing diets, except for the lowest dose (250 ppm), significantly reduced female birthrate.


Citations (55)


... Aside from increase in target biological signal biofeedback, experience may influence some psychological traits such as alexithymia [29,30] and promote improvements through these changes. Peniston et al. [31] and Klee and Meyer [32] discussed an impact on a learned helplessness as a possible factor of depression improvement with biofeedback. Biofeedback teaches patients that they can avoid aversive stimuli, which is controversial to a learned helplessness mindset and is in line with a self-efficacy mindset. ...

Reference:

The Current Evidence Levels for Biofeedback and Neurofeedback Interventions in Treating Depression: A Narrative Review
EMG Biofeedback-Assisted Relaxation Training in the Treatment of Reactive Depression in Chronic Pain Patients
  • Citing Article
  • October 1986

The Psychological Record

... A similar insensitivity of the observed behavior can be seen in the lack of decrease in observed drinking after CCK-8 in the ethanol group, although intake reliably decreased. This lack of correlation of observed drinking and ethanol intake after CCK-8 injection has been reported earlier (Kulkosky, Sanchez, & Glazner, 1986), and it has been explained by the decreased licking efficiency reported after CCK-8 injection (Hsiao & Spencer, 1983). Caffeine consumption was also associated with an increase in high activity behaviors, which gives evidence of an effective stimulant action of the oral caffeine. ...

Cholecystokinin octapeptide: Effect on the ethogram of ethanol consumption and blood ethanol levels in the rat
  • Citing Article
  • January 1986

... The most common clinical reaction caused by psoralens is linear hyperpigmentation in areas of exposure to the agent, which can be persistent for weeks and even months (Brancaccio and Alvarez 2004). The threshold for toxicity in humans regarding furanocoumarins was determined to be 1800 μg/100 g fresh weight of the plant (parsley), for developing acute dermatitis and 700 to 900 μg/100 g, for repeated or chronic exposures, which may range for different parts of the body (Diawara and Kulkosky 2003;Diawara et al. 1997). The results of this study were expressed in dry weight and they might be lower if they were expressed in fresh weight. ...

Mammalian toxicity of 5-methoxypsoralen and 8-methoxypsoralen, two compounds used in skin photochemotherapy
  • Citing Article
  • June 1997

Journal of Natural Toxins

... 2 Taste disorder is a common observation in diabetes mellitus type 1 patients 3 and type 2 patients 4 with a significant and somewhat specific impairment in sweet taste detection. 5,6 Previous studies reported a direct effect of blood glucose concentration on taste. 3 However, some investigators found no correlation between taste and either the plasma glucose or the glycosylated hemoglobin concentration. ...

Afferent receptors, taste percpetion and pacnreatic endocrine endocrine function in man
  • Citing Article
  • January 1975

Diabetes

... Any medically prescribed substances were taken into consideration during the interpretation of the qEEG results. Medications were also considered for the development of treatment protocols as well as the Peniston protocol and the Scott-Kaiser modification (Dousset et al., 2020;Peniston & Kulkosky, 1989, 1990Scott & Kaiser, 1998). ...

Alcoholic personality and alpha-theta brainwave training
  • Citing Article
  • January 1990

... Neurofeedback therapy has shown promising outcomes in treating posttraumatic stress disorder (Chiba et al., 2019). Peniston and Kulkosky (1991) conducted experimental research with patients suffering from war-related chronic PTSD, revealing significant reductions in somatic symptoms, depression, anxiety, paranoia, and overall PTSD symptoms following neurofeedback treatment. ...

Alpha-theta brainwave neuro-feedback therapy for Vietnam veterans with combat-related post-traumatic stress disorder
  • Citing Article
  • January 1991

... Their work focused on theta over alpha enhancement at occipital brain regions after applying skin temperature training and breathing exercises. They observed positive outcomes mainly in personality variables, dosage of medication, prolongation of abstinence, and prevention of relapses (Peniston and Kulkosky, 1989, 1993. Although the precise mechanisms of alpha-theta training remain elusive (Gruzelier and Egner, 2005), two possible explanations were formulated: (1) training leads to a cross-over state (theta exceeds over alpha rhythm) which contributes to psychological integration (Peniston and Kulkosky, 1993) and (2) counteracting the increase in beta-endorphin levels induced by stress of abstinence (Peniston and Kulkosky, 1989). ...

EEG alpha-theta brainwave synchronization in Vietnam theater veterans with combat-related post-traumatic stress disorder and alcohol abuse
  • Citing Article
  • January 1993

... It IS clear from the data that presentation of a previously poisoned solution on a stable baseline of schedule-induced drinking results in a substantial but relatively short-duration suppression of consumption. The initial suppression of schedule-induced drinking is similar in degree to suppression of waterdeprivation-induced or stimulation-bound drinking (Garcia & Ervin, 1968;Kulkosky et al., 1975;Wise & Albin, 1973). However, the rapid recovery of drinking the previously poisoned solution is quite unlike the prolonged suppression typically seen in the extinction of conditioned taste aversions (Ader, 1973;Braveman, 1974;Garcia et al., 1969). ...

Interaction of brain stimulation and conditioned taste aversion: Osmotically induced drinking
  • Citing Article
  • Full-text available
  • September 1975

Physiological Psychology

... In a later study, Peniston reported that during AT sessions in which visual imagery was reported, significant amplitude increases occurred in both the theta and beta ranges but not in the EEG alpha band. Follow-up measures after 13 months demonstrated significant lower relapse rates in the experimental NF group compared to the control group (CG) (Peniston and Kulkosky 1999). In recent studies, after 12 NF sessions, an increase in the alpha and theta bands occurred, and this increase was associated with decreased avoidant and stressrelated personality traits (Dalkner et al. 2017) and clinical changes (Lackner et al. 2016) in patients with AUD. ...

Neurofeedback in the Treatment of Addictive Disorders
  • Citing Chapter
  • December 1999