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  • 1
    Electronic Resource
    Electronic Resource
    Does crossing over repeated treatment with the dopamine reuptake inhibitors cocaine and BTCP modify their effects on cocaine-induced locomotion? (1999)
    Springer
    Psychopharmacology 143 (1999), S. 8-14 
    Details
    ISSN: 1432-2072
    Keywords: Key words Sensitization ; Reverse tolerance ; Tolerance ; Withdrawal ; Cocaine ; BTCP ; Locomotion ; Dopamine reuptake inhibitor ; Psychostimulant ; Dopamine transporter ; Addiction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Because the dopamine reuptake inhibitors cocaine and BTCP produce different behavioral effects after repeated administration, we studied whether they could alter each other’s effects by examining the effects of crossing over repeated treatment with cocaine and BTCP on cocaine-induced locomotion. Male C57BL/6 mice were treated repeatedly with cocaine or BTCP during a first phase (days 1–3) and 3 days later, treated repeatedly with the same or the other compound during a second phase (days 7–9), after which they were administered one of several doses of cocaine on the next day. Locomotor activity was assessed after every daily treatment. The results show that 1) cocaine induced sensitization to its locomotor effects, 2) cocaine-induced sensitization was not altered by subsequent repeated treatment with BTCP, 3) initial repeated treatment with BTCP induced apparent cross-tolerance to cocaine, and 4) the initial effects of repeated BTCP were not markedly altered by subsequent repeated treatment with cocaine. The results indicate that the initial effects produced by repeated cocaine or BTCP are enduring and relatively difficult to alter by crossing over repeated treatment with the other compound. Thus, sensitization to the locomotor effects of cocaine in mice appeared to be attenuated by prior repeated treatment with BTCP but not reversed when followed by repeated treatment with BTCP.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050912
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  • 2
    Electronic Resource
    Electronic Resource
    Interactions between neuroleptics and 5-HT1A ligands in preclinical behavioral models for antipsychotic and extrapyramidal effects (1999)
    Springer
    Psychopharmacology 144 (1999), S. 20-29 
    Details
    ISSN: 1432-2072
    Keywords: Key words Schizophrenia ; Extrapyramidal side-effect ; Neuroleptic ; Antipsychotic ; Dopamine D2 receptor ; Serotonin 5-HT1A receptor ; Intrinsic activity ; Paw test ; Catalepsy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rationale: Combining neuroleptics with 5-HT1A ligands is thought to improve the preclinical profile of neuroleptics and may be of interest in the development of new compounds that have greater therapeutic potential and/or are better tolerated. Objective: To examine 1) the ability of 5-HT1A ligands to alter the effects of neuroleptics in preclinical models for antipsychotic potential (hindlimb retraction time in the paw test) and extrapyramidal side-effects (forelimb retraction time in the paw test; catalepsy tests), 2) the role of intrinsic activity at 5-HT1A receptors in the modulatory effects of 5-HT1A ligands, and 3) the generality of the interactions across neuroleptics. Methods: The effects of different doses of 5-HT1A ligands with intrinsic activity ranging from high (e.g., 8-OH-DPAT) to low (e.g., WAY 100135) administered together with a fixed, high dose of the neuroleptics haloperidol, risperidone, and tropapride were examined in the paw test and on catalepsy. Results: Firstly, the 5-HT1A agonists 8-OH-DPAT and ipsapirone attenuated the extrapyramidal-like effects of haloperidol and risperidone more than their therapeutic-like effects; this was not observed for tropapride, where all of its effects were markedly attenuated. Secondly, neither the weak 5-HT1A agonist WAY 100135 nor the silent antagonist WAY 100635 attenuated the effects of neuroleptics. Thirdly, neuroleptics apparently differed in their sensitivity to interactions with 5-HT1A agonists inasmuch as 8-OH-DPAT and ipsapirone attenuated the effects of tropapride on hindlimb retraction times more than those of haloperidol or risperidone. Conclusions: The present data suggest that 5-HT1A agonists with intermediate or high, but not low, intrinsic activity may abolish the extrapyramidal effects of neuroleptics. Together with results of previous studies, it appears that 5-HT1A agonists alter the antipsychotic-like effects of neuroleptics, although this may depend on the neuroleptic studied.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050972
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  • 3
    Electronic Resource
    Electronic Resource
    Repeated administration of cocaethylene induces context-dependent sensitization to its locomotor effects (1996)
    Springer
    Psychopharmacology 124 (1996), S. 300-305 
    Details
    ISSN: 1432-2072
    Keywords: Cocaine ; Dopamine reuptake blockers ; Reverse tolerance ; Convulsions ; Context-dependency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The cocaine analog, cocaethylene, has recently been identified as an active metabolite in humans consuming ethanol and cocaine. Since this compound exhibits affinity for the dopamine transporter that is more selective than that of cocaine, it is conceivable that its behavioral properties may be distinguishable from those of cocaine (cf. Elsworth et al. 1993). To investigate further the behavioral effects of cocaethylene, its ability to induce sensitization to locomotor activity in C57BL/6 mice was determined and compared with that of cocaine. In the first part of the study, mice were treated repeatedly with cocaethylene in the test environment and were then challenged with several different doses of the same drug. Repeated administration of 10, 20 or 40 mg/kg cocaethylene (IP) for 3 consecutive days produced leftward and upward shifts of the cocaethylene (2.5–56.6 mg/kg, IP) doseeffect curve on day 4. In the second part of the study, mice were treated with 20 mg/kg cocaethylene for 3 days, but were immediately placed back in their home cage following the injection: repeated administration of cocaethylene for 3 consecutive days did not significantly affect the dose-effect curve of cocaethylene (2.5–40 mg/kg, IP) on day 4. In the same paradigm, repeated administration of 20 mg/kg cocaine for 3 consecutive days produced a significant leftward shift of the cocaine (2.5–56.6 mg/kg, IP) dose-effect curve on day 4. These results confirm that cocaethylene shares a number of properties with cocaine, but also suggest that the drugs are not identical.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02247434
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  • 4
    Electronic Resource
    Electronic Resource
    Effects of dopamine antagonists in a two-way active avoidance procedure in rats: interactions with 8-OH-DPAT, ritanserin, and prazosin (1996)
    Springer
    Psychopharmacology 128 (1996), S. 191-197 
    Details
    ISSN: 1432-2072
    Keywords: Key words Schizophrenia ; Neuroleptics ; Dopamine D2 receptor ; Serotonin 5-HT2 receptor ; α1-Adrenoceptor ; Conditioned avoidance response ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Using a conditioned avoidance procedure in rats, the present study examined the ability of 8-OH-DPAT, ritanserin, and prazosin to alter the effects of the dopamine antagonists, raclopride and haloperidol, on avoidance- and on escape responding. The 5-HT1A agonist 8-OH-DPAT (0.16 mg/kg) significantly enhanced the inhibitory effects of both raclopride and haloperidol on the conditioned avoidance response and produced a small enhancement of the effects of haloperidol on escape failures. The α1-adrenoceptor antagonist prazosin (0.63 mg/kg) significantly enhanced the effects of raclopride on the conditioned avoidance response, but enhanced the effects of only a single dose of haloperidol; prazosin did not alter the effects of either dopamine antagonist on escape failures. The 5-HT2 antagonist ritanserin (0.16 mg/kg) failed significantly to alter the effects of the dopamine antagonists examined here. These findings suggest that blockade of 5-HT2 receptors may not enhance the antipsychotic efficacy of D2-like antagonists. Further, they confirm previous findings with respect to interactions between 5-HT1A agonists and neuroleptics, and support the hypothesis that combined 5-HT1A agonist/D2-like antagonist properties may be of clinical importance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050124
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  • 5
    Electronic Resource
    Electronic Resource
    The olfactory tubercle as a site of action of neuroleptics with an atypical profile in the paw test: effect of risperidone, prothipendyl, ORG 5222, sertindole and olanzapine (1995)
    Springer
    Psychopharmacology 119 (1995), S. 428-439 
    Details
    ISSN: 1432-2072
    Keywords: Atypical neuroleptics ; N. accumbens ; Olfactory tubercle ; Paw test ; Locomotor activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The paw test was used to detect the preclinical profile (classical versus atypical) of five putative, atypical neuroleptics, namely olanzapine, sertindole, risperidone, prothipendyl and ORG 5222. In the paw test classical neuroleptics increase the hindlimb reaction time (HRT), a parameter with predictive validity for antipsychotic efficacy, at doses comparable to those necessary for increasing forelimb reaction time (FRT), a parameter with predictive validity for extrapyramidal side-effects, whereas atypical neuroleptics increase HRT at doses that are much smaller than those increasing FRT. All tested compounds showed the profile of atypical neuroleptics in the paw test. Using the FRT/HRT ratio of minimum effective doses as overall predictor of a favourable ratio of extrapyramidal and therapeutic effects of these drugs, the following order was found: olanzapine (20) 〉 sertindole = risperidone = prothipendyl (10) 〉 ORG 5222 (3). The ability of compounds to attenuate locomotor activity elicited either from the olfactory tubercle (10 µg dopamine: OT test) or from the nucleus accumbens (1 µg ergometrine: ACC test) was used to establish whether the compounds preferentially act in one of these structures. Previous research has shown that classical neuroleptics are far less potent in the OT test than in the ACC test, whereas atypical neuroleptics are far more potent in the OT test than in the ACC test. All five agents preferentially acted in the olfactory tubercle. The order of potency in the olfactory tubercle was as follows: sertindole 〉 ORG 5222 〉 risperidone 〉 olanzapine 〉 prothipendyl. It is concluded that risperidone, prothipendyl, ORG 5222, sertindole and olanzapine not only show the profile of atypical neuroleptics in the paw test, but also preferentially act in the olfactory tubercle, but not in the nucleus accumbens, viz. two features that they share with the atypical neuroleptics clozapine and thioridazine and with the putative, atypical neuroleptics raclopride and remoxipride.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245859
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