Psychopharmacology

Bürki, H.; Asper, H.; Ruch, W.; Züger, P.

doi: 10.1007/BF00426743pmid: 97702

213 57 57 3 3 H. R. Bürki H. Asper W. Ruch P. E. Züger Research Institute Wander Ltd. P.O. Box 2747 CH-3001 Berne Switzerland the Biological and Medical Research Division Sandoz Ltd. Basle Switzerland Abstract The effects of the ergolene derivatives bromocriptine, dihydroergotoxine, methysergide, d-LSD, CF 25-397, and 29-712 on the metabolism of the biogenic amines in the brain of the rat were investigated. All six ergolene derivatives were found to increase the concentration of 4-hydroxy-3-methoxyphenylethylene glycol sulphate in the brain stem, i.e., to increase the turnover of noradrenaline (NA). Since in brain homogenates the agents inhibited the binding of 3 H-dihydroergocryptine to α-adrenoceptors, but only weakly inhibited the binding of 3 H-alprenolol to β-adrenoceptors, it is suggested that the increased turnover of NA may be a consequence of a blockade of α-adrenoceptors by ergolenes. All of the ergolenes increased the concentration of serotonin (5-HT) in the cortex, but only bromocriptine and 29-712 increased the concentration of 5-hydroxyindoleacetic acid (5-HIAA), the other compounds decreasing the concentration of this metabolite, i.e., inhibiting 5-HT turnover. Reserpine-induced PGO waves in the cat were inhibited by all six compounds, bromocriptine and 29-712 being the least active. Both of these findings suggest that the ergolenes possess serotonergic activity. The increase in the concentration of 5-HIAA after bromocriptine and 29-712 may be secondary to some action on other systems. The actions of the ergolenes on the metabolism of dopamine (DA) in the striatum are more complex. Bromocriptine, 29-712, and, to a much lesser extent, dihydroergotoxine reduced the concentration of 3,4-dihydroxyphenylacetic acid (DOPAC), i.e., they inhibited DA turnover. These findings are compatible with the proposed dopaminergic activity of the drugs. CF 25-397 caused a slight increase in the DOPAC concentration at high doses, and d-LSD and methysergide caused pronounced increases. At doses below 1 mg/kg i.p., d-LSD decreased the DOPAC concentration. This biphasic effect of d-LSD may be due to interaction with different types of DA receptors or may reflect some secondary action of the compound. The profiles of activity of the various ergolenes are discussed. Bromocriptine and 29-712, wich have similar profiles of activity, can be clearly differentiated from the other ergolenes. CF 25-397 seems to be a potent and, at low doses, specific serotonergic drug.

Frankel, David; Khanna, Jatinder; Kalant, Harold; LeBlanc, A.

doi: 10.1007/BF00426744pmid: 149992

213 57 57 3 3 David Frankel Jatinder M. Khanna Harold Kalant A. Eugene LeBlanc Department of Pharmacology University of Toronto, and Addiction Research Foundation of Ontario M5S 1A8 Toronto Canada Abstract Daily administration of ethanol in a liquid diet or by intubation were both effective in producing tolerance to the hypothermic effects of ethanol. When p -chlorophenylalanine ( p -CPA) was administered in a dose previously demonstrated to maintain extensive brain serotonin (5-HT) depletion, the temperature-lowering effects of ethanol were less pronounced than in corresponding controls. The analysis of the effect of p -CPA on tolerance development took into account both initial body temperature and the degree of hypothermia. This study extends our findings with respect to the inhibitory effect of p -CPA on the development of tolerance to the motor-impairing effects of ethanol, and suggests that 5-HT may have a role in tolerance development to ethanol.

Bloom, Alan; Dewey, William

doi: 10.1007/BF00426745pmid: 97703

213 57 57 3 3 Alan S. Bloom William L. Dewey Department of Pharmacology, Medical College of Virginia Virginia Commonwealth University 23298 Richmond Virginia USA Department of Pharmacology Medical College of Wisconsin 53233 Milwaukee Wisconsin USA Abstract The effects of morphine and Δ 9 -tetrahydrocannabinol (THC) on the tail-flick reflex, body temperature, and catecholamine synthesis were examined in the mouse in order to compare their effects in a single species and strain under uniform conditions. Naloxone antagonism of THC and cross-tolerance between morphine and THC were also studied. Both morphine and THC produced antinociception, hypothermia, and increased catecholamine synthesis at 30 min after s.c. injection. Morphine produced greater increases in dopamine synthesis and was a more potent antinociceptive agent, while THC produced greater increases in norepinephrine synthesis and was a more potent hypothermic agent. Naloxone pretreatment (1 mg/kg) partially antagonized the hypothermia and increase in catecholamine synthesis produced by THC. There was also crosstolerance between morphine and THC, but it was asymmetric in that THC-tolerant animals were crosstolerant to only the hypothermic action of morphine and morphine-tolerant animals cross-tolerant to only the antinociceptive action of THC.

Yehuda, Shlomo; Frommer, Reuven

doi: 10.1007/BF00426746pmid: 97704

213 57 57 3 3 Shlomo Yehuda Reuven Frommer Department of Psychology, Psychopharmacology Laboratory Bar-Ilan University Ramat-Gan Israel Abstract Exposing a rat's tail to an ambient temperature lower than that sensed by the rest of the body causes an increase in body temperature. Pretreatment with d -amphetamine causes an even greater increase in body temperature. Moreover, while control rats perceive any ambient temperature below 20° C as ‘cold’, amphetamine-treated animals only perceive ambient temperatures below 20° C as “cold”. This effect of d -amphetamine was found not only when the body temperature of the rats was 20° C, but also when the body was kept at ambient temperatures of 15°-4° C. Because this effect of d -amphetamine, i.e., shifting of the reference point among treated rats, was found in two other situations (behavioral thermoregulation and in studying the anorexic effects of d -amphetamine among rats kept at different ambient temperatures), the best explanation is that in addition to the effects of the drug upon some thermal sensory roles, it also causes a change in the value of the set point of the thermoregulatory system, and drug-treated rats perceive ambient temperatures of 10° C as ‘normal’.

Gryll, Steven; Katahn, Martin

doi: 10.1007/BF00426747pmid: 97705

213 57 57 3 3 Steven L. Gryll Martin Katahn Waterbury Hospital USA Vanderbilt University USA Merriman Hall, Team II Waterbury Hospital Health Center 06720 Waterbury Connecticut USA Abstract The influence of four variables (status of communicator of drug effects, attitude of dentist, attitude of dental technician, and message of drug effects) on the obtainment of placebo effects in an oral surgery clinic was investigated. Dependent variables were (1) rating of pain experienced from mandibular-block injection, (2) pre-post placebo state anxiety, and (3) pre-postplacebo fear of injection. Enthusiastic messages of drug effects produced statistically and clinically significant reductions in postplacebo fear of injection and state anxiety and markedly lower ratings of pain experienced during injection of local anesthetic. Although there was a strong tendency for positive placebo effects to occur when the dental staff was perceived as friendly and supportive, only the attitude factors obtained statistical significance. The status of the communicator accounted for very small portions of the variance.

Walton, Nancy; Roll, Phillip; Thiel, Thomas; Rogers, Joseph

doi: 10.1007/BF00426748pmid: 97706

213 57 57 3 3 Nancy Y. Walton Phillip L. Roll Thomas R. Thiel Joseph Rogers Department of Psychology, C-009 University of California, San Diego 92093 La Jolla California USA Abstract Evidence is presented that learned safety increases the rat's willingness to drink ethanol; induction of tolerance to ethanol following learned safety training produces a further increase. Rats with chronically implanted intragastric fistulae consumed substantially more (30%) alcohol when aversive post-ingestional effects were minimized by draining stomach contents during drinking than did rats allowed to retain stomach contents. Half the rats from each group were then made tolerant by prolonged forced alcohol intubation. Later testing showed an increase in alcohol consumption by rats receiving learned safety training or rendered tolerant, with the two factors being additive.

Morris, Michael; Gebhart, G.

doi: 10.1007/BF00426749pmid: 97707

213 57 57 3 3 Michael D. Morris G. F. Gebhart Department of Pharmacology, College of Medicine University of Iowa 52242 Iowa City Iowa USA Department of Psychology Coe College 52402 Cedar Rapids IA USA Abstract Rats were trained on an appetitive discretetrial discriminated-punishment task in which they learned to suppress responding when an intense flashing light predicting punishment was present and to respond rapidly on trials when the flashing light was absent. Once animals were performing discriminatively, 0.75, 3.0, or 6.0 mg/kg of morphine (base) was administered and a fear extinction session consisting of 60 nonshocked presentations of the flashing light was given. Two saline control groups, one that received fear extinction and one that did not, were also included in the experiment. On the day following fear extinction, all rats were tested in the undrugged state on the discriminated punishment problem, but without shock. The rats receiving 3.0 and 6.0 mg/kg of morphine before the fear extinction session were suppressed by the flashing light more than the saline extinction group or the 0.75 mg/kg morphine treatment group. Moreover, the two higher dose morphine groups were suppressed as readily as the saline group that received no fear extinction. These results are attributed to the antiemotionality effects of morphine.

Carlson, Kristin; Almasi, John

doi: 10.1007/BF00426750pmid: 97708

213 57 57 3 3 Kristin R. Carlson John Almasi Department of Pharmacology University of Pittsburgh School of Medicine 15261 Pittsburgh Pennsylvania USA Department of Pharmacology University of Massachusetts Medical School 55 Lake Avenue North 01605 Worcester MA USA Abstract Male albino guinea pigs were treated for 3 weeks with methadone, morphine, haloperidol, or saline. One week and 5 weeks following termination of treatment they were challenged with the directly acting dopaminergic agonist apomorphine. At the week 1 test the haloperidol and saline groups did not differ, but behavioral supersensitivity was apparent in significantly elevated mean stereotypy scores of the methadone and morphine groups relative to the saline group. The source of differences in mean scores was a higher peak score rather than increased duration of action. At the week 5 test the scores of the methadone group were even higher, the morphine group's scores were equivalent to the saline group's, and the haloperidol group's scores were significantly depressed. This study indicates that a 3-week treatment period with methadone or morphine is sufficient to induce dopaminergic supersensitivity and suggests that there may be different time courses for the retention or expression of supersensitivity following these narcotics.

Carlson, Kristin; Almasi, John

doi: 10.1007/BF00426751pmid: 97709

213 57 57 3 3 Kristin R. Carlson John Almasi Department of Pharmacology University of Pittsburgh School of Medicine 15261 Pittsburgh Pennsylvania USA Department of Pharmacology University of Massachusetts Medical School 55 Lake Avenue North 01605 Worcester MA USA Abstract Male albino guinea pigs aged 4–10 weeks were challenged with 0.1, 0.2, and 0.4 mg/kg apomorphine. Mean stereotypy scores rose significantly as a function of age. Stereotypy scores were better correlated with age than with body weight, suggesting that CNS maturation, rather than weight-related factors, was responsible. Although age and body weight were correlated, there was enough variability to make body weight an unreliable indicator of age.

Glick, Stanley; Cox, Russell

doi: 10.1007/BF00426752pmid: 97710

213 57 57 3 3 Stanley D. Glick Russell D. Cox Department of Pharmacology, Mount Sinai School of Medicine City University of New York Fifth Avenue and 100th Street 10029 New York New York USA Abstract Rats were trained to bar-press for intravenous infusions of morphine sulfate during 1-h daily test sessions. Rates of moprhine self-administration were enhanced by lesions of the frontal cortex and hippocampus and transiently reduced by lesions of the medial forebrain bundle and medial thalamus. Doseresponse studies indicated that sensitivity to morphine's rewarding property was decreased by frontal cortical and hippocampal lesions. Lesions of the posterior cortex, the tuberculum olfactorium, and the nucleus accumbens had no effect on self-administration behavior. The results are discussed in relation to previous findings with caudate and brainstem lesions. A neuroanatomical substrate for morphine reinforcement is suggested.