Social influences on morphine sensitization in adolescent rats

Activities of the endocannabinoid system are believed to be substantially involved in psychostimulant and opioid addiction. Nevertheless, interactions between cannabinoid and opioid systems are not yet fully understood. Thus, the aim of the present study was to investigate the interaction between morphine and the cannabinoid CB 1 receptor agonist arachidonylcyclopropylamide (ACPA) in behavioural sensitisation. Sensitisation occurs after repeated exposure to drugs of abuse including morphine and cannabinomimetics and it has been suggested to mediate craving and relapses. Male mice were randomly allocated into three groups and were seven times (from the 7 th to 13 th day of the experiment) administered drugs as follows: (a) n 1 : vehicle at the dose of 10 ml/kg/day; (b) n 2 : morphine at the dose of 10.0 mg/kg/day; (c) n 3 : ACPA at the dose of 1.0 mg/kg/day. Changes in locomotor behaviour were measured in the Open Field Test: (a) after administration of vehicle on the 1 st experimental day, (b) after the 1 st dose of drugs given on the 7 th day, and (c) on the 14 th day after "challenge doses" given in the following way: n 1 : saline at the dose of 10 ml/kg, n 2, 3 : morphine at the dose of 10.0 mg/kg. Registered behavioural changes unambiguously showed the development of behavioural sensitisation to the stimulatory effects of morphine on locomotion after its repeated administration (P < 0.05). However, surprisingly, taking into account reports on synergistic effects of opioids and cannabinoid receptor stimulation, a significant decrease (P < 0.05) in behavioural sensitisation to morphine occurred when the drug challenge dose was given following repeated pre-treatment with the CB 1 receptor agonist ACPA, i.e. suppression of cross-sensitisation to morphine. Keywords

Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 99%

Interaction of CB<sub>1</sub> receptor agonist arachidonylcyclopropylamide with behavioural sensitisation to morphine in mice

Landa¹,

Šlais²,

Máchalová³

et al. 2014

“…This phenomenon is termed behavioural sensitisation and was described for the first time by Robinson and Berridge (1993). Behavioural sensitisation occurs not only for psychostimulants -amphetamine (Enman and Unterwald 2012;Fukushiro et al 2012) or cocaine (Aracil-Fernandez et al 2012;Ramos et al 2012) but also for other psychotropic substances -e.g., morphine (Hofford et al 2012;Niu et al 2012), delta(9)-tetrahydrocannabinol (Cadoni et al 2008), ethanol (Bahi and Dreyer 2012) and nicotine (Lee et al 2012).…”

mentioning

confidence: 99%

The effect of sertindole on behavioural sensitisation to methamphetamine in mice

Landa¹,

Šlais²,

Šulcová³

2012

Similarly to various other addictive substances, methamphetamine (Met) produces, following repeated application, a strong increase in behavioural responses (particularly locomotor behaviour), a phenomenon termed behavioural sensitisation. In our previous studies we tested the effects of various psychotropic drugs on behavioural sensitisation to Met, particularly the effects of cannabinoid receptor ligands with different intrinsic activities and felbamate and memantine, antagonists of N-methyl-d-aspartate (NMDA) receptors. In the present study we investigated the influence of the antipsychotic drug sertindole (Srt) on sensitisation to the effects of Met on mouse locomotor behaviour in the Open field test. Male mice were randomly divided into 4 groups and were administered drugs seven times (from the 7 th to 13 th day of the experiment) as follows: (a) n 1, 2 : Met at the doses of 2.5 mg/kg/day; (b) n 3 :Met + Srt at the doses of 2.5 mg/kg/day + 10.0 mg/kg/day; (c) n 4 : Srt at the dose of 10.0 mg/kg/day. Locomotion in the Open field test was measured (a) after administration of vehicle on the 1 st day, (b) after the 1 st dose of drugs given on the 7 th day, and (c) on the 14 th day after the "challenge doses" administered in the following way: n 1 : Met; n 2 : Met+Srt, n 3 : Met; n 4 : Srt. We found the following significant behavioural changes: (1) a stimulatory influence of Met and development of sensitisation after repeated treatment (n 1 ); (2) an inhibition of Met sensitisation in the case of a combined challenge dose of Met + Srt (n 2 ); (3) a stimulatory effect of Met when animals were repeatedly pre-treated with Met + Srt (n 3 ); (4) a significant inhibition of locomotion after the 1 st dose of Srt, that persisted even after the last Srt dose (n 4 ). Data concerning the involvement of sertindole in reward processes associated with drug addiction are not completely consistent and our results reflect this ambiguity to a certain extent. A combined challenge dose of Met + Srt administered after repeated pre-treatment with Met inhibited the development of behavioural sensitisation; on the other hand a Met challenge dose alone administered after repeated pre-treatment with Met + Srt produced a significant increase in locomotion.Keywords: behavioural sensitisation; methamphetamine; sertindole; mice List of abbreviations AM 251 = N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide,JWH 015 = 1 propyl-2-methyl-3-(1-naphthoyl)indole, Met = methamphetamine, NMDA = N-methyl-d-aspartate, Srt = sertindole, V = vehicle

“…This phenomenon was observed after repeated administration of both legal and illegal drugs and has been described for ethanol (Broadbent 2013;Kim and Souza-Formigoni 2013;Linsenbardt and Boehm 2013), nicotine (Hamilton et al 2012;Lenoir et al 2013;Perna and Brown 2013), caffeine (Zancheta et al 2012), cannabinoids (Rubino et al 2003;Cadoni et al 2008), psycho-stimulants (Landa et al 2006a,b;2012a,b;Wang et al 2010;Ball et al 2011;Kameda et al 2011) or opioids (Bailey et al 2010;Liang et al 2010;Farahmandfar et al 2011;Hofford et al 2012;Rezayof et al 2013).…”

mentioning

confidence: 99%

The effect of the cannabinoid CB1 receptor agonist arachidonylcyclopropylamide (ACPA) on behavioural sensitisation to methamphetamine in mice

Landa¹,

Šlais²,

Máchalová³

et al. 2014

ABSTRACT:The psychostimulant methamphetamine (Met), similarly to other drugs of abuse, is known to produce an increased behavioural response after its repeated application (behavioural sensitisation). It has also been described that an increased response to a drug may be elicited by previous repeated administration of another drug (cross-sensitisation). We have previously shown that the CB 1 , CB 2 and TRPV (vanilloid) cannabinoid receptor agonist methanandamide, cross-sensitised to Met stimulatory effects in mice. The present study was focused on ability of the more selective and potent CB 1 receptor activator arachidonylcyclopropylamide (ACPA) to elicit cross-sensitisation to the stimulatory effects of Met on mouse locomotor behaviour in the Open field test. Male mice were randomly divided into three groups and on seven occasions (from the 7 th to 13 th day of the experiment) were administered drugs as follows:(a) n 1 : vehicle at the dose of 10 ml/kg/day; (b) n 2 : Met at the dose of 2.5 mg/kg/day; (c) n 3 : ACPA at the dose of 1.0 mg/kg/day. Locomotor behaviour in the Open field test was measured (a) after administration of vehicle on the 1 st experimental day, (b) after the 1 st dose of drugs given on the 7 th day, and (c) on the 14 th day after the "challenge doses" administered in the following manner: n 1 : saline at a dose of 10 ml/kg, n 2, 3 : Met at a dose of 2.5 mg/kg. The observed behavioural changes consisted in: (a) gradual development of habituation to the open field conditions in three consecutive tests; (b) development of behavioural sensitisation to the stimulatory effects of Met after repeated treatment; (c) insignificant effect of repeated pre-treatment with ACPA on the stimulatory effects of Met challenge dose. The results of our study give rise to the question which of the cannabinoid receptor mechanisms might be most responsible for the neuroplastic changes inducing sensitisation to the stimulatory effects of Met. Keywords