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- Johnson, D H, et al.
(författare)
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Induction but not expression of behavioural sensitization to nicotine in the rat is dependent on glucocorticoids.
- 1995
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Ingår i: European journal of pharmacology. - 0014-2999. ; 276:1-2, s. 155-64
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Tidskriftsartikel (refereegranskat)abstract
- Behavioural sensitization has been implicated in the development of addictive behaviour, and several studies suggest that corticosteroids may be involved in this phenomenon. In the present study, the effects of adrenalectomy and steroid replacement treatments on the behavioural sensitization observed after daily injections of nicotine (0.4 mg/kg s.c.) were investigated in the rat. Adrenalectomy completely prevented sensitization to the locomotor stimulating effect of nicotine after repeated injections but did not influence the acute locomotor activating effect of the drug or an already established sensitization to nicotine. In adrenalectomized animals receiving replacement treatment with corticosterone or dexamethasone, but not aldosterone, repeated administration of nicotine produced behavioural sensitization. Repeated dexamethasone treatment per se failed, however, to sensitize rats to nicotine. Post mortem neurochemical studies showed that repeated administration of nicotine significantly increased homovanillic acid (HVA) levels, as well as the dihydroxyphenylacetic acid (DOPAC)/dopamine quotient, in the limbic forebrain. Adrenalectomy per se significantly increased HVA levels and tended to elevate the DOPAC/dopamine quotient. When repeatedly treated with nicotine, adrenalectomized rats displayed a higher DOPAC/dopamine quotient, but no significant difference in HVA levels, compared to nicotine-treated sham-operated controls. In the striatum and the cortex, no significant effects of nicotine treatment or adrenalectomy were observed on any of the neurochemical measures. The present results suggest that glucocorticoid (type II) receptor activation is required for induction of sensitization to the locomotor stimulatory effect of nicotine, whereas corticosteroids are not required for the expression of the behavioural sensitization once established. Provided that HVA levels and the DOPAC/dopamine quotient relatively well reflect the presynaptic dopamine activating effect of nicotine, it may be suggested that corticosteroid-related mechanisms associated with behavioural sensitization to nicotine are post- rather than presynaptically located in relation to mesolimbic dopamine neurons.
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| 2. |
- Söderpalm, Bo, 1959, et al.
(författare)
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Naloxone reverses disinhibitory/aggressive behavior in 5,7-DHT-lesioned rats; involvement of GABA(A) receptor blockade?
- 1999
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Ingår i: Neuropharmacology. - 0028-3908. ; 38:12, s. 1851-9
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Tidskriftsartikel (refereegranskat)abstract
- Effective medical treatment for impulsive aggression and several impulse control disorders is needed. Disinhibited, impulsive behavior of e.g. murderers, arsonists, suicidal patients, and patients suffering from antisocial personality or substance abuse disorders has been associated with signs of a deficiency in brain serotonin (5-HT) systems. Depletion of brain 5-HT consistently produces disinhibition and aggression also in experimental animals. The present series of experiments using a modified Vogel's conflict test indicates that the disinhibitory behavior of 5-HT-lesioned rats can be reversed by the commonly used opiate receptor antagonist naloxone at doses (0.1-5.0 mg/kg, s.c.) that do not significantly affect behavior in sham-lesioned controls. Moreover, this effect of naloxone, which resembles that previously observed after administration of negative modulators of gamma-aminobutyric acidA (GABA(A))/benzodiazepine receptor complexes, was reversed by a low inert dose (2.0 mg/kg, i.p.) of amobarbital. Furthermore, both naloxone (5.0 mg/kg, s.c.) and Ro 15-4513 (1.0 mg/kg, p.o.; a partial inverse agonist at benzodiazepine receptors) significantly decreased the number of attacks and the time spent in aggressive acts in 5,7-DHT-lesioned male residents. These results taken together with previous behavioral and neurochemical data suggest that the behavioral effects of naloxone observed here may involve an antagonistic action at brain gamma-aminobutyric acidA (GABA(A))/benzodiazepine receptor complexes. Thus, naloxone, its stable analogue naltrexone or other weak negative modulators of brain GABA(A)/benzodiazepine receptor complexes may represent a new pharmacological principle for the treatment of impulse control disorders.
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| 3. |
- Zhang, Jianhua, 1961, et al.
(författare)
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Repeated administration of amphetamine induces sensitisation to its disruptive effect on prepulse inhibition in the rat.
- 1998
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Ingår i: Psychopharmacology. - 0033-3158. ; 135:4, s. 401-6
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Tidskriftsartikel (refereegranskat)abstract
- Male Sprague-Dawley rats were repeatedly treated with amphetamine (AMP, 1 mg/kg, SC) at 3- day intervals for 15 days and tested for prepulse inhibition of acoustic startle after each treatment. This treatment regimen induced sensitisation in the animals as evidenced by a progressive increase in the disruptive effect of AMP on prepulse inhibition. Persistent changes in brain function was indicated, since an increase in disruptive effect was observed in sensitised animals also after a 22-day-long drug- and test-free period. The development of sensitisation was blocked by pretreatment with haloperidol (HPD, 0.1 mg/kg, SC), which suggests that sensitisation to the disruptive effect of AMP was dependent on dopamine (DA) D2 receptor activation. Furthermore, the development of sensitisation was blocked by adrenalectomy, which suggests that sensitisation was dependent also on circulating adrenal hormones. Increased DA-ergic activity has been implicated in the pathophysiology of schizophrenia and AMP-induced sensitisation to the neuronal functions that modulate prepulse inhibition may be an experimental model to investigate this hypothesis.
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