Chronic Exposure to WIN55,212-2 During Adolescence Alters Prefrontal Dopamine Turnover and Induces Sensorimotor Deficits in Adult Rats.

Several lines of evidence suggest that chronic exposure to cannabinoids during adolescence may increase the risk of schizophrenia. Studies of the disorder have identified altered cortical dopaminergic neurotransmission. In this study, we hypothesised that heightened endocannabinoid system activation via chronic exposure to a highly potent cannabinoid receptors agonist in adolescent rats would cause long-lasting neurobiological changes that may dramatically alter expression and functions of dopamine metabolising enzymes, comethyl-o-transferase (COMT) and monoamine oxidases MAO-A and MAO-B. To test this hypothesis, adult male rats (70 PND) undergoing chronic treatment of the highly potent and non-selective CB agonist WIN55,212-2 (1.2 mg/kg) during adolescence (PND 30-50) were subjected after 20 days washout period to prepulse inhibition of acoustic startle test (PPI) to confirm cannabinoid-induced sensorimotor-gating impairments and afterwards examined for COMT, MAO-A and MAO-B expression and activity in the prefrontal cortex. Chronic WIN55,212-2 exposure during adolescence caused disruption of PPI, increased cortical dopamine level, decreased COMT mRNA expression and decreased MAO-A and MAO-B enzymatic activities. These results indicate that chronic exposure to cannabinoids during adolescence induces sensorimotor-gating alterations which likely result from changes in the prefrontal cortex dopaminergic signalling. This has important implications for developing methods of targeting dopamine metabolising enzymes and/or sequelae of its dysregulation in cannabinoid-induced schizoaffective-like behaviour.

Nicotine-Cadmium Interaction Alters Exploratory Motor Function and Increased Anxiety in Adult Male Mice.

In this study we evaluated the time dependence in cadmium-nicotine interaction and its effect on motor function, anxiety linked behavioural changes, serum electrolytes, and weight after acute and chronic treatment in adult male mice. Animals were separated randomly into four groups of n = 6 animals each. Treatment was done with nicotine, cadmium, or nicotine-cadmium for 21 days. A fourth group received normal saline for the same duration (control). Average weight was determined at 7-day interval for the acute (D1-D7) and chronic (D7-D21) treatment phases. Similarly, the behavioural tests for exploratory motor function (open field test) and anxiety were evaluated. Serum electrolytes were measured after the chronic phase. Nicotine, cadmium, and nicotine-cadmium treatments caused no significant change in body weight after the acute phase while cadmium-nicotine and cadmium caused a decline in weight after the chronic phase. This suggests the role of cadmium in the weight loss observed in tobacco smoke users. Both nicotine and cadmium raised serum Ca(2+) concentration and had no significant effect on K(+) ion when compared with the control. In addition, nicotine-cadmium treatment increased bioaccumulation of Cd(2+) in the serum which corresponded to a decrease in body weight, motor function, and an increase in anxiety.