Search

Abstract: Adult C57BL/6 mice received uni- or bilateral cryogenic or sham-lesions over the barrel field and their exploratory behaviour was assessed in an open field between 1 and 7 days post-lesion. Bilateral cortical lesions produced a short-lasting increase in thigmotactic scanning with both sides of the face on the first day of testing. Mice with a unilateral barrel-cortex lesion showed more contralateral wall scanning with a recovery to behavioural symmetry after 5–7 days. Furthermore, the increase in contralateral thigmotaxis was most pronounced in animals with damage to the left barrel field, indicative of a lateralization of the lesion-induced behavioural changes. The cortical lesions did not influence locomotor activity and the rate of habituation to the open field (habituation ‘learning’). Referring to recent electrophysiological findings, we hypothesize that the lesion established a lateralized source of increased neuronal excitability within the affected barrel-cortex, leading to more behaviour with its corresponding vibrissae. Alternatively, if the lesion results in contralateral ‘neglect’ in terms of input, the increased scanning with the affected vibrissae may reflect an attempt of the system to compensate for this with an increase in usage. [Copyright &y& Elsevier]

Abstract: The CB1 cannabinoid receptor has been implicated in the control of fear and anxiety. We investigated the effects of genetic and pharmacological blockade of the CB1 cannabinoid receptor on the behaviour of CD1 mice using three different ethological models of fear and anxiety (elevated T-maze and plus-maze and open field test of emotionality). Furthermore, we measured tissue levels of noradrenalin (NA), dopamine (DA), serotonin (5-HT) and their metabolites in several forebrain regions, i.e. prefrontal cortex, hippocampus, septum, dorsal and ventral striatum to examine the relationship between CB1 receptor manipulation and monoaminergic neurotransmission. The major findings can be summarized as follows: The CB1 receptor antagonist SR141617A (rimonabant) modulated anxiety in a dose-dependent manner. At a dose of 3mg/kg i.p., the compound consistently increased anxiety parameters in all of the three different anxiety tests applied, while a lower dosage of 1mg/kg had no such effect. The neurochemical evaluation of the mice administered 3mg/kg SR141617A revealed increases in the concentrations of DOPAC and 5-HIAA in the dorsal striatum, elevated DA levels in the hippocampus and reduced dopamine turnover in the septum. Furthermore, these animals had a higher HVA/DA turnover in the frontal cortex. CB1 receptor knockout mice as well as mice treated with the selective CB1 receptor antagonist AM251 (3mg/kg; i.p.) did not display any significant alterations in anxiety-related behaviour as measured with the elevated plus-maze and open field test of emotionality, respectively. Our findings support the general idea of a SR141617A-sensitive receptive site that is different from the ‘classical’ CB1 receptor and that has a pivotal role in the regulation of different psychological functions. However, with regard to its functional significance in terms of anxiety our findings suggest that under physiological conditions this receptive site seems to be involved in the control of anxiolysis rather than anxiogenesis as suggested previously. [Copyright &y& Elsevier]

Abstract: Endogenous cannabinoids modulate the activity of dopamine reward pathways and may play a role in the development of behavioural sensitization to psychostimulants. Here, we investigated the effects of the CB1 cannabinoid receptor antagonist AM251 on amphetamine-induced locomotor sensitization in mice. Furthermore, we measured post-mortem monoamine concentrations in nucleus accumbens and hippocampus after termination of the behavioural tests. The results can be summarized as follows: Mice pre-treated with AM251 (3 mg/kg; i.p.) showed less sensitivity to the psychomotor stimulant as well as locomotor sensitizing effects of amphetamine (2 mg/kg; i.p.) resembling previous results obtained with CB1 receptor-deficient animals. Furthermore, the behavioural effects of AM251 were paralleled by increased dopamine concentration in nucleus accumbens and increased serotonin concentration/turnover rate in hippocampus, respectively. The present data indicate that under normal conditions activation of the CB1 receptor facilitates those adaptive responses elicited by repeated psychostimulant administration and resulting in sensitization, possibly by reducing dopamine biosynthesis and serotonin turnover in the nucleus accumbens and hippocampus. [Copyright &y& Elsevier]

Abstract: Cannabinoid receptors and their endogenous ligands (endocannabinoids) have been implicated in cocaine and amphetamine reward. Their role in psychostimulant-induced behavioural sensitization still has to be determined. The purpose of the present study was, for one, to compare the effects of a pharmacological and genetic manipulation of CB1 cannabinoid receptors on amphetamine-induced locomotor sensitization in mice, and, secondly, to quantify the concentration of anandamide and 2-arachidonoylglycerol in different forebrain areas of behaviourally sensitized animals. The results can be summarized as follows: CB1 knockout mice failed to sensitize to the locomotor stimulant effects of amphetamine. On the contrary, administration of the CB1 receptor antagonist SR141716A (rimonabant; 3mg/kg; i.p.) increased amphetamine sensitization in wild-type animals, indicating that the difference between CB1 knockouts and SR141716A treated animals could be due to the ‘chronic’ versus ‘acute’ loss of CB1 receptor function, or, alternatively, that SR141716A could exert pharmacological effects beyond its proposed CB1 antagonistic action. Furthermore, sensitized wild-type mice and animals, which had received a single amphetamine injection on the challenge day, both had increased anandamide concentrations in the dorsal striatum and decreased anandamide levels in the ventral striatum, comprising nucleus accumbens. 2-Arachidonoylglycerol levels were decreased in the ventral striatum of sensitized animals only. Together, these findings suggest that prolonged activation of dopamine receptors could alter endocannabinoid levels and support the proposed involvement of the CB1 receptor in amphetamine sensitization. [Copyright &y& Elsevier]

We reported previously that the glycosaminoglycan heparin (HP) has the facility to improve learning in adult rodents when administered into the nucleus basalis of the ventral pallidum. Here we gauged the effects of chronic intraventricular infusion of HP (20 ng per day over 28 days) in 26-month-old rats in terms of Morris water maze performance, habituation to a novel open field, retention of a step-through inhibitory avoidance task and changes in forebrain acetylcholine (ACh) levels. Control groups included vehicle-infused old and adult (3-month-old) rats. The chronic infusion of HP did not significantly influence the performance of the old animals in any of the learning and memory tasks employed. HP only slightly facilitated the retention of the inhibitory avoidance task and the rate of habituation in the open-field paradigm. In the water maze, the glycosaminoglycan did not counteract the navigation deficits observed for aged controls and even impaired performance during the initial place-learning trials. After behavioural testing, tissue levels of ACh were determined in frontal cortex, ventral striatum, neostriatum and hippocampus without detecting any obvious neurochemical differences between groups. The current results, together with our previous work, indicate that HP differentially affects learning and memory parameters in adult and aged rats. Thus, whereas the glycosaminoglycan proved effective in facilitating mnemonic functions in normal adult animals, no such a clear-cut beneficial effect was observed in behaviourally impaired old rats. [Copyright &y& Elsevier]