Psychopharmacology

Cooper, Steven

doi: 10.1007/BF00433244pmid: 6779317

213 71 71 1 1 Steven J. Cooper Department of Psychology University of Birmingham P.O. Box 363 B15 2TT Birmingham England Abstract Naloxone (0.5–5 mg/kg) reduced both food and water intake in non-deprived male rats, tested in the dark phase of the light-dark cycles in their home cages. These effects were transient; food and water-intake were restored to control levels by the end of the 8-h test period. The effects were also not dose-related. Naloxone (1 and 5 mg/kg) also reduced water-intake in water-deprived and food-deprived animals, without altering food-intake. These results suggested that naloxone may exert a primary antidipsogenic action, that does not depend upon any suppression of feeding. A final experiment showed that naloxone can completely abolish the thirst produced by injection of a hypertonic saline solution. This experiment also demonstrated that naloxone could suppress feeding, even though food intake was markedly inhibited by the osmotic thirst stimulus. Hence, the activation of feeding responses (e.g. by food deprivation) is not a necessary condition for naloxone to suppress feeding. The implications of these results for the control of feeding and drinking responses are briefly considered.

Spissu, A.; Congia, S.; Piccardi, M.; Fadda, F.; Mangoni, A.; Gessa, G.

doi: 10.1007/BF00433245pmid: 6161384

213 71 71 1 1 A. Spissu S. Congia M. P. Piccardi F. Fadda A. Mangoni G. L. Gessa Clinica delle Malattie Nervose e Mentali Università di Cagliari Via Porcell 4 I-09100 Cagliari Italy Istituto di Farmacologia Università di Cagliari Via Porcell 4 I-09100 Cagliari Italy Abstract The effect of tiapride on HVA and 5-HIAA levels in the CSF drawn at pneumoencephalography (PEG) was studied. Five consecutive 5 ml fractions of CSF were drawn from control and tiapride-treated subjects. In both groups, a linear increase in HVA concentrations was found between the first and subsequent fractions. On the contrary, no significant difference in 5-HIAA concentrations was found in sequential CSF samples. Tiapride increased the mean HVA concentrations and caused a steeper caudocranial gradient of this metabolite but failed to modify 5-HIAA concentrations. The results suggest that tiapride blocks dopamine (DA) receptors and increases DA synthesis.

Linseman, Mary; Grupp, Larry

doi: 10.1007/BF00433246pmid: 6779320

213 71 71 1 1 Mary Ann Linseman Larry A. Grupp Neurobiology Section Addiction Research Foundation 33 Russell Street M5S 2S1 Toronto Ontario Canada Abstract Medial thalamic (MT), and hippocampal (HPC) EEG, and single unit activity, and frontal cortical (CTX) EEG were recorded following IV infusions of 0.625 mg morphine/kg in drug-naive, and following 0.0125 mg naloxone/kg in morphine-dependent paralyzed rats. Particular effort was made to assess the latency of the responses in relation to the appearance of high-voltage bursts in the CTX EEG (which has been shown to correlate well with the behavioral state of the animal) and thereby to assess the possible primacy of the effects. In MT, the predominant effect of morphine on units of naive animals was a decrease in activity; that of naloxone in dependent animals, an increase in activity. Morphine decreased theta activity in the MT EEG, while naloxone precipitated theta activity. In the case of morphine, the majority of unit changes preceded CTX EEG changes; in the case of naloxone, most MT unit and EEG changes either coincided with or followed the changed CTX EEG. In contrast, HPC units were relatively unresponsive to morphine, but the HPC EEG often showed marked spiking following the infusion that generally preceded the appearance of spindles in the CTX. Naloxone caused increases and decreases in HPC unit activity, but these changes as well as those of the HPC EEG (also to theta) generally followed corresponding changes in the CTX EEG. The possibility that both areas might be primary sites of action of morphine, but not naloxone, was discussed.

Herling, Seymore; Valentino, Rita; Winger, Gail

doi: 10.1007/BF00433247pmid: 6779321

213 71 71 1 1 Seymore Herling Rita J. Valentino Gail D. Winger Departments of Pharmacology and Psychology University of Michigan 48109 Ann Arbor Michigan USA Abstract Pigeons were trained to discriminate the IM injection of pentobarbital (5 or 10 mg/kg) from saline in a task in which 20 consecutive pecks on one of two response keys produced access to mixed grain. Pentobarbital (1.0–17.8 mg/kg) produced a dose-related increase in the percentage of the total session responses that occurred on the pentobarbital-appropriate key. The concomitant administration of bemegride (5.6–17.8 mg/kg) antagonized the discriminative control of behavior exerted by the training dose of pentobarbital. Benzodiazepines, diazepam (1.0 mg/kg) and clobazam (3.2 mg/kg), and barbiturates, methohexital (10 mg/kg), phenobarbital (56 mg/kg), and barbital (56 mg/kg), produced responding on the pentobarbital-appropriate key similar to that produced by pentobarbital. In contrast, narcotics such as morphine, ethylketazocine, cyclazocine, and SKF-10,047, at doses up to and including those that markedly suppressed response rates, produced responding predominantly on the saline-appropriate key. Similarly, the anticonvulsants, valproate, phenytoin, and ethosuximide occasioned only saline-appropriate behavior, indicating that not all anticonvulsants share discriminative stimulus effects with pentobarbital. Muscimol, a direct GABA agonist, and baclofen, a structural analogue of GABA, also failed to produce pentobarbital-appropriate responding. Ketamine, dextrorphan, and ethanol (0.3–3.2 g/kg, orally) produced intermediate levels of pentobarbital-appropriate responding, suggesting that the discriminative effects of these drugs may be somewhat like those of pentobarbital.

Gardos, George; Samu, Istvan; Kallos, Maria; Cole, Jonathan

doi: 10.1007/BF00433248pmid: 6109346

213 71 71 1 1 George Gardos Istvan Samu Maria Kallos Jonathan O. Cole Boston State Hospital, IRR-323 591 Morton Street 02124 Boston Massachusetts USA Neuropsychiatric Clinic Salgótarján 1 Bajcsi Zs-u. Hungary McLean Hospital 115 Mill Street 02178 Belmont Massachusetts USA Abstract One hundred and twenty-two patients comprising 82% of the non-hospitalized schizophrenic population of a Hungarian town were rated for tardive dyskinesia (TD). Drug histories were also obtained. No severe cases of TD were found. The markedly lower prevalence of TD in the study population in contrast to similar North American samples may be related to differences in treatment styles, in particular to: a) use of EST in place of high-dose neuroleptic therapy; b) extensive exposure to ethopropazine, promethazine, and other antiparkinson drugs. Twenty patients revealed clinically evident fine tremors, mostly of the tongue and eye-lid. Multivariate analysis revealed a positive association of choreiform dyskinesia with duration of low-potency neuroleptic treatment.

Turski, Lechosław; Kleinrok, Zdzisław

doi: 10.1007/BF00433249pmid: 6779322

213 71 71 1 1 Lechosław Turski Zdzisław Kleinrok Department of Pharmacology Institute of Clinical Pathology Medical School Jaczewskiego 8 PL 20-090 Lublin Poland Abstract Intraventricular (IV) administration of doses of 0.1 μg kainic acid caused diphasic effects on the body temperature of rats — initially hypothermia, rapidly followed by hyperthermia. Pretreatment of rats with 6-OHDA effectively blocked the hypothermic and significantly increased the hyperthermic effects of kainic acid. The hyperthermic effect of kainic acid was reversed in the 5,6-DHT- and dorsal raphe-lesioned rats. However, the electrolytic lesion of the medial raphe nucleus did not cause any changes in the thermic activity of kainic acid. The thermic effects of kainic acid injected IV appear to be dependent on the balance between serotonergic and catecholaminergic influences on central thermoregulation.

File, Sandra

doi: 10.1007/BF00433250pmid: 6779323

213 71 71 1 1 Sandra E. File Department of Pharmacology, The School of Pharmacy University of London Brunswick Square WC1N 1AX London England Abstract Naloxone (1,2, and 4 mg/kg) produced a dose-related decrease in exploratory head-dipping in rats placed singly in a holeboard for 10 min, without a concomitant reduction in locomotor activity. Naloxone (2 mg/kg) reduced the time spent in active social interaction by pairs of rats tested in an unfamiliar or in a familiar test arena, and also reduced the amount of motor activity shown by the pairs of rats. The results are consistent with proposed roles for opiate peptides in behavioural responses to novel environments and in mediating social contact.

Hatchell, Patricia; Collins, Allan

doi: 10.1007/BF00433251pmid: 6779324

213 71 71 1 1 Patricia C. Hatchell Allan C. Collins Institute for Behavioral Genetics and School of Pharmacy University of Colorado Boulder Colorado USA Department of Biology University of Missouri-Kansas City 64110 Kansas City Missouri USA Abstract The influences of genotype and sex on spontaneous motor activity in a Y-maze after nicotine administration and on nicotine concentrations in liver and brain were assessed in three inbred mouse strains. The rank order of liver nicotine elimination rates in these strains was found to be C57>C3H=DBA for females and DBA>C3H=C57 for males. Within the C57 and C3H strains, females eliminated nicotine significantly faster than males, while DBA females and males eliminated nicotine at similar rates. The rank order of motor depression at early time points after nicotine administration was found to be DBA=C57>C3H for both males and females. Females of all three strains demonstrated less sensitivity to nicotine's depressant effects than males. There did not appear to be any consistent association between rate of liver nicotine elimination or brain nicotine level and motor depression as measured in the Y-maze. Although variability in liver nicotine elimination and in brain nicotine content may account for some of the observed behavioral effects, these data suggest that strain and sex differences in tissue sensitivity to nicotine are of primary importance.

Mucha, R.; Kalant, H.

doi: 10.1007/BF00433252pmid: 6779325

213 71 71 1 1 R. F. Mucha H. Kalant Department of Pharmacology University of Toronto and Addiction Research Foundation of Ontario M5S 2S1 Toronto Canada Abstract Rats injected (IP) daily with 0, 20, and 200 mg/kg morphine-SO 4 for 25–49 days experienced log dose/response (LDR) curve flattening (decrease in slope and/or maximum response) for analgesia (tail immersion test) produced by etorphine-HCl injected IP or intracerebroventricularly (ICV), and for latency to maximum rectal temperature increase produced by IP etorphine. Rats treated similarly with 0, 50, and 500 μg/kg etorphine-HCl for 32 days exhibited LDR-curve flattening for analgesia produced by etorphine and morphine (IP). In addition, a profound body weight loss produced by high-dose morphine treatment (200 mg/kg) was found not to be involved in flattening, since similar body weight decreases produced by food restriction in 0 and 20 mg/kg rats did not have this effect. Flattening, however, may be due to a rapidly acquired and rapidly lost within-session (acute) tolerance. When flattening was not seen at short intervals after IP or ICV test etorphine doses, flattening was seen when rats were retested at longer test intervals. Forty-eight hours after cessation of chronic etorphine treatment, flattening of the etorphine analgesia LDR curve was lost, but parallel shift was unaffected. Similarly, 200 mg/kg morphine-treated rats lost morphine tolerance more rapidly than 20 mg/kg-treated rats during the first 12 days after the last treatment injection. Subsequently, however, levels of the analgesia and the amounts of tolerance loss were comparable in both chronically treated groups. The data support the notion that chronic tolerance reflects an enhancement or prolongation of acute tolerance.

Sansone, Mario

doi: 10.1007/BF00433253pmid: 6109347

213 71 71 1 1 Mario Sansone Istituto di Psicobiologia e Psicofarmacologia C. N. R. via Reno I-00198 Roma Italy Abstract Four benzodiazepine tranquilizers have been tested, alone or in combination with amphetamine, on spontaneous locomotor activity of C57BL/6 mice. Amphetamine-induced locomotor stimulation was enhanced by chlordiazepoxide, diazepam, and medazepam, but not by bromazepam. The results indicate that benzodiazepine derivatives may be somewhat differentiated on the basis of their interactions with amphetamine.