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Striatal adenosine-dopamin modulation in morphine dependence and withdrawal
69
0-10 Obsessive Compulsive Disorder including depression, anxiety, cocaine withdrawal, and eating disorders. Previous experiments in our lab showed that intra-cerebroventricular (icv) NPY strongly inhibits the generation of wet dog shakes (WDS) which accompany hippocampal EEG seizures after focal electrical stimulation. WDS are also known to be associated with withdrawal from morphine. This prompted us to study a possible effect of NPY on morphine withdrawal. Rats were injected subcutaneously with morphine for four days with increasing doses. On the last day, morphine withdrawal was precipitated with naloxone (10 mglkg, i.p.) 30 min after an icv injection of NPY (3, 6, or 12 nmol) or vehicle and withdrawal signs were observed for 2 h. The intensity of the withdrawal reaction was assessed by a point scoring technique modified by weighting the signs. The score included motor-related signs (e.g. WDS, head shakes, jumping, writhing, teeth chattering) and non motor-related signs (e.g. irritability, genital licking, weight loss). NPY potently and dose-dependently reduced the withdrawal score by 50-75%. This effect resulted from an attenuation of motoras well as non-motor-related signs. Specifically, NPY almost completely abolished the occurrence of WDS. Whether this effect of NPY is related to its inhibitory effects on seizure-related WDS remains to be established, as does the site of action of NPY on morphine withdrawal. However, the present data suggest that NPY ergic neurotransmission deserves attention with regard to mechanisms of and therapeutic potential in morphine dependence.
I0-9-91
[I] [2] [3] [4] [5] [6]
Lewis JWet al., NIDA Res.Monogr. 90 (1988) 136-143. ZemigG et al.,Analgesia (1995) in press. ZemigG et al., NIDA Res. Monogr. (1995) in press. Fibiger He, Sem. Neurosci. 5 (1993) 321-327. Wise RAet al.,Synapse 21 (1995) 140-148. Damsma Getal.,Behav. Neurosci. 106 (1992) 181-191.
10.10 I Obsessive Compulsive Disorder
I0-10-1 I PanicAttack as an Epi-Phenomenon of the Phobic-Obsessive-CompuIsiveDisease
Striatal Adenosine-Dopamin Modulation in Morphine Dependence and Withdrawal
Y.-P.Liu, D.- T. Bau, N.-K. Hwang, P.-M. Chen, w-r. Liu, c.s. Tung. Military Psychiatry Center, Taipei, R.O.C.; Dept. ofPhysiology. NDMC, Taipei, R.O.C. The present study investigated the possible modulatory effect of adenosine on dopamine system in the conditions of morphine dependence and withdrawal. By i.p, injection, the male Sprague-Dawley rats received increasing loading doses of morphine (5 to 50 mglkg) in first 5 days and naloxone (5 mglkg) on the 6th day. In vivo microdialysis with microbore-HPLCIECD was used to study the changes of dopamine and its metabolites. Capillary electrophoresis was used to examine the adenosine metabolites, inosine and hypoxanthine. We also monitored the locomotor activity and several stereotyped behaviors such as jumping, wet-dog shaking, tail sweeping, teeth chattering and yawning. We found that in morphine dependence, locomotor activity and stereotyped behaviors attenuated, striatal extracellular dopamine and its metabolites increased, and the adenosine metabolites mildly changed. In morphine withdrawal, the adenosine metabolites increased apparently, the behaviors were intensified but dopamine and its metabolites decreased. We suggested that striatal dopamine system was modulated in different manners by adenosine system according to the conditions of morphine dependence or withdrawal.
I0-9-10 I Cloclnnamox Inhibits Heroin-Stimulated Nucleus Accumbens Dopamine Overflow
G. Zemig, H.C. Fibiger. Division ofNeurological Sciences, Department of Psychiatry, University ofBritish Columbia, Vancouver, Canada The cinnamoylaminomorphinone clocinnamox (CCAM [I]), a pseudoirreversible mu-opioid receptor ligand [2], insurmountably antagonizes mu opioid agonist self-administration in rhesus monkeys [3]. The present study tested the effects of clocinnamox on heroin-stimulated overflow of dopamine in the nucleus accumbens in awake, freely moving animals, a neurobiochemical measure of the unconditioned effects of drugs of abuse [4] which also occurs during self-administration of heroin [5]. Male Wistar rats were implanted with in vivo microdialysis probes in the nucleus accumbens (NAC) and tested for extracellular levels of dopamine (DA) and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillie acid (HVA) 48 h later by online HPLC-electrochemical detection in 10 min bins [6]. CCAM (10 mglkg; n = 4) or vehicle (VEH; 1% lactic 3) was injected 24 h prior to the microdialysis experiment acid; n during which a saline administration was followed 20 min later by heroin (0.5 mglkg). All injections were given subcutaneously. CCAM had no significant effect on basal release of DA (4.8 ± 0.6 fmol/min), DOPAC
=
(946 ± 76 fmol/min), or HVA (408 ± 12 fmol/min). Saline injections did not produce any changes in overflow of DA, DOPAC, or HVA in either the VEH or CCAM group. Heroin increased DA overflow to a maximum of 179 ± 7% of baseline 40 min after its injection. CCAM blocked this effect almost completely, reducing DA overflow to 114 ± 4% of baseline. Accordingly, CCAM also blocked heroin-stimulated overflow of DOPAC (VEH peak at 50 min, 173 ± 17%; CCAM, J 16 ± 4%) and HVA (VEH peak at 70 min, 200 ± 33%; CCAM, 122 ± 7%). Thus, CCAM almost completely blocked the heroin-stimulated release of DA and its metabolites in the NAC without affecting their basal levels. CCAM was generously provided by Dr. J.H. Woods.
C.R. Hejaij. lntra-Hospitalar Psychiatric Unit, Samaritano Hospital, sao Paulo, Brazil Panic attack is a new designation for the very old anguish crisis (or attack). As it is an acute manifestation, the diagnosis is usually made through the state picture (transversal cut). The persistence of this sole diagnostic perspective leads to misunderstandings because it ignores the possible insertion of the anguish crisis in a long course mental disorder. Therefore, one must considerer a diagnosis that takes into account the history of the disease, a longitudinal perspective. On the other hand, in anguish crises a concurrence of other symptoms is frequently verified, which, in according to a methodological principle of Medicine, must be all considered, initially, as belonging to a sole disease. The clinical history of several patients with anguish attacks reveals the presence of old phobic and obsessive symptoms, as well as other depressive features, characterizing the Phobic-Obsessive-Compulsive Disease in the overall. This work intends to demonstrate the importance of the longitudinal view in Psychiatry through the characterization of the Anguish Attack as an epiphenomenon of the Phobic-Obsessive-Compulsive Disease.
1
0-10-21 Biological and Psychopathological Comparison of OCDandTourette Syndrome
N. Milller, A. Putz, M. Riedel, N. Kathmann, A. Straube I. Psychiatric Hospital, Ludwig-Maximilian-University Munich; I Department of Neurology, Ludwig-Maximilian-University Munich A high prevalence of obsessions and compulsions is recognized in patients with Tourette-syndrome (TS). A comparison of a group of patients with TS and another with OCD, using the DSM III-R criteria showed significantly higher scores in obsessions and compulsions than a control group. However, it was possible to show specific differences of obsessive compulsive symptoms in OCD and in Tourette syndrome [I]. This investigation was repeated in other groups of GTS- and OCD patients. The results of the cross-validation will be presented. Moreover, we performed neuroendocrinological tests in both groups of patients. Since in OCD an alteration of the serotonergic neurotransmission is likely, we performed the fenfluramine-test in both groups of patients. Own investigations have shown, that in TS the growth hormone response to clonidine is blunted, these results pointing to a disturbance in the noradrenergic neurotransmission in GTS [2]. Therefore we compared the clonidine-test in 10 patients with OCD and 10 patients with TS. The results of the psychopathologic and neuroendocrine investigations, pointing to a psychopathological and pathophysiological difference between OCD and GTS will be presented. l l l N. Miiller, A. Putz, A. Straube, N, Kathmann: Obsessive compulsive disorders andGilles-de-la-Tourette-Syndrome. Differential diagnosis of organic and psychicobsessions andcompulsions. Nervenarzt 66: 372-378, 1995
0-10 Obsessive Compulsive Disorder including depression, anxiety, cocaine withdrawal, and eating disorders. Previous experiments in our lab showed that intra-cerebroventricular (icv) NPY strongly inhibits the generation of wet dog shakes (WDS) which accompany hippocampal EEG seizures after focal electrical stimulation. WDS are also known to be associated with withdrawal from morphine. This prompted us to study a possible effect of NPY on morphine withdrawal. Rats were injected subcutaneously with morphine for four days with increasing doses. On the last day, morphine withdrawal was precipitated with naloxone (10 mglkg, i.p.) 30 min after an icv injection of NPY (3, 6, or 12 nmol) or vehicle and withdrawal signs were observed for 2 h. The intensity of the withdrawal reaction was assessed by a point scoring technique modified by weighting the signs. The score included motor-related signs (e.g. WDS, head shakes, jumping, writhing, teeth chattering) and non motor-related signs (e.g. irritability, genital licking, weight loss). NPY potently and dose-dependently reduced the withdrawal score by 50-75%. This effect resulted from an attenuation of motoras well as non-motor-related signs. Specifically, NPY almost completely abolished the occurrence of WDS. Whether this effect of NPY is related to its inhibitory effects on seizure-related WDS remains to be established, as does the site of action of NPY on morphine withdrawal. However, the present data suggest that NPY ergic neurotransmission deserves attention with regard to mechanisms of and therapeutic potential in morphine dependence.
I0-9-91
[I] [2] [3] [4] [5] [6]
Lewis JWet al., NIDA Res.Monogr. 90 (1988) 136-143. ZemigG et al.,Analgesia (1995) in press. ZemigG et al., NIDA Res. Monogr. (1995) in press. Fibiger He, Sem. Neurosci. 5 (1993) 321-327. Wise RAet al.,Synapse 21 (1995) 140-148. Damsma Getal.,Behav. Neurosci. 106 (1992) 181-191.
10.10 I Obsessive Compulsive Disorder
I0-10-1 I PanicAttack as an Epi-Phenomenon of the Phobic-Obsessive-CompuIsiveDisease
Striatal Adenosine-Dopamin Modulation in Morphine Dependence and Withdrawal
Y.-P.Liu, D.- T. Bau, N.-K. Hwang, P.-M. Chen, w-r. Liu, c.s. Tung. Military Psychiatry Center, Taipei, R.O.C.; Dept. ofPhysiology. NDMC, Taipei, R.O.C. The present study investigated the possible modulatory effect of adenosine on dopamine system in the conditions of morphine dependence and withdrawal. By i.p, injection, the male Sprague-Dawley rats received increasing loading doses of morphine (5 to 50 mglkg) in first 5 days and naloxone (5 mglkg) on the 6th day. In vivo microdialysis with microbore-HPLCIECD was used to study the changes of dopamine and its metabolites. Capillary electrophoresis was used to examine the adenosine metabolites, inosine and hypoxanthine. We also monitored the locomotor activity and several stereotyped behaviors such as jumping, wet-dog shaking, tail sweeping, teeth chattering and yawning. We found that in morphine dependence, locomotor activity and stereotyped behaviors attenuated, striatal extracellular dopamine and its metabolites increased, and the adenosine metabolites mildly changed. In morphine withdrawal, the adenosine metabolites increased apparently, the behaviors were intensified but dopamine and its metabolites decreased. We suggested that striatal dopamine system was modulated in different manners by adenosine system according to the conditions of morphine dependence or withdrawal.
I0-9-10 I Cloclnnamox Inhibits Heroin-Stimulated Nucleus Accumbens Dopamine Overflow
G. Zemig, H.C. Fibiger. Division ofNeurological Sciences, Department of Psychiatry, University ofBritish Columbia, Vancouver, Canada The cinnamoylaminomorphinone clocinnamox (CCAM [I]), a pseudoirreversible mu-opioid receptor ligand [2], insurmountably antagonizes mu opioid agonist self-administration in rhesus monkeys [3]. The present study tested the effects of clocinnamox on heroin-stimulated overflow of dopamine in the nucleus accumbens in awake, freely moving animals, a neurobiochemical measure of the unconditioned effects of drugs of abuse [4] which also occurs during self-administration of heroin [5]. Male Wistar rats were implanted with in vivo microdialysis probes in the nucleus accumbens (NAC) and tested for extracellular levels of dopamine (DA) and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillie acid (HVA) 48 h later by online HPLC-electrochemical detection in 10 min bins [6]. CCAM (10 mglkg; n = 4) or vehicle (VEH; 1% lactic 3) was injected 24 h prior to the microdialysis experiment acid; n during which a saline administration was followed 20 min later by heroin (0.5 mglkg). All injections were given subcutaneously. CCAM had no significant effect on basal release of DA (4.8 ± 0.6 fmol/min), DOPAC
=
(946 ± 76 fmol/min), or HVA (408 ± 12 fmol/min). Saline injections did not produce any changes in overflow of DA, DOPAC, or HVA in either the VEH or CCAM group. Heroin increased DA overflow to a maximum of 179 ± 7% of baseline 40 min after its injection. CCAM blocked this effect almost completely, reducing DA overflow to 114 ± 4% of baseline. Accordingly, CCAM also blocked heroin-stimulated overflow of DOPAC (VEH peak at 50 min, 173 ± 17%; CCAM, J 16 ± 4%) and HVA (VEH peak at 70 min, 200 ± 33%; CCAM, 122 ± 7%). Thus, CCAM almost completely blocked the heroin-stimulated release of DA and its metabolites in the NAC without affecting their basal levels. CCAM was generously provided by Dr. J.H. Woods.
C.R. Hejaij. lntra-Hospitalar Psychiatric Unit, Samaritano Hospital, sao Paulo, Brazil Panic attack is a new designation for the very old anguish crisis (or attack). As it is an acute manifestation, the diagnosis is usually made through the state picture (transversal cut). The persistence of this sole diagnostic perspective leads to misunderstandings because it ignores the possible insertion of the anguish crisis in a long course mental disorder. Therefore, one must considerer a diagnosis that takes into account the history of the disease, a longitudinal perspective. On the other hand, in anguish crises a concurrence of other symptoms is frequently verified, which, in according to a methodological principle of Medicine, must be all considered, initially, as belonging to a sole disease. The clinical history of several patients with anguish attacks reveals the presence of old phobic and obsessive symptoms, as well as other depressive features, characterizing the Phobic-Obsessive-Compulsive Disease in the overall. This work intends to demonstrate the importance of the longitudinal view in Psychiatry through the characterization of the Anguish Attack as an epiphenomenon of the Phobic-Obsessive-Compulsive Disease.
1
0-10-21 Biological and Psychopathological Comparison of OCDandTourette Syndrome
N. Milller, A. Putz, M. Riedel, N. Kathmann, A. Straube I. Psychiatric Hospital, Ludwig-Maximilian-University Munich; I Department of Neurology, Ludwig-Maximilian-University Munich A high prevalence of obsessions and compulsions is recognized in patients with Tourette-syndrome (TS). A comparison of a group of patients with TS and another with OCD, using the DSM III-R criteria showed significantly higher scores in obsessions and compulsions than a control group. However, it was possible to show specific differences of obsessive compulsive symptoms in OCD and in Tourette syndrome [I]. This investigation was repeated in other groups of GTS- and OCD patients. The results of the cross-validation will be presented. Moreover, we performed neuroendocrinological tests in both groups of patients. Since in OCD an alteration of the serotonergic neurotransmission is likely, we performed the fenfluramine-test in both groups of patients. Own investigations have shown, that in TS the growth hormone response to clonidine is blunted, these results pointing to a disturbance in the noradrenergic neurotransmission in GTS [2]. Therefore we compared the clonidine-test in 10 patients with OCD and 10 patients with TS. The results of the psychopathologic and neuroendocrine investigations, pointing to a psychopathological and pathophysiological difference between OCD and GTS will be presented. l l l N. Miiller, A. Putz, A. Straube, N, Kathmann: Obsessive compulsive disorders andGilles-de-la-Tourette-Syndrome. Differential diagnosis of organic and psychicobsessions andcompulsions. Nervenarzt 66: 372-378, 1995