Biopsychology and Learning Behavioral Enhancement

Question: Discuss about the Biopsychology and Learning Behavioral Enhancement. Answer: Introduction: Methamphetamine is an illicit substance required by most of the people in Australia to produce high or a rush in their body. Use of methamphetamine in Australia is more than doubled in last five years. Major contribution to the increased use of methamphetamine is population between 15-24 years (NIT, 2015). Methamphetamine comes under Schedule 8 prohibited substance in Australia under the Poisons Standard (July 2016). In many countries manufacturing, sale and possession of methamphetamine is prohibited and it is illegal in most of the jurisdictions. United Nations Convention on Psychotropic Substances treaty has placed methamphetamine in schedule II. Methamphetamine hydrochloride is a potent full antagonist of the trace amine-associated receptor 1 (TAAR1) (Xie Miller, 2009). This TAAR1 is a G protein-coupled receptor (GPCR) and it regulates catecholamine (epinephrine, norepinephrine, and dopamine) level in the central nervous systems. Activation of TAAR1 by the action of methamphetam ine increases second messenger cyclic adenosine monophosphate (cAMP) release and there is the inhibition or reversal of transport direction of the dopamine transporter (DAT), norepinephrine transporter (NET), and serotonin transporter (SERT) (Miller, 2011). Methamphetamine inhibit or reverses action of monoamines because binding of methamphetamine with TAAR1 results in the phosphorylation of transporter through protein kinase A (PKA) and protein kinase C (PKC) signaling and consequently there is the internalization or reversal of the function of monoamine trasnsportes. Methamphetamine also increases level of intracellular calcium and it is responsible for the phosphorylation of DAT through Ca2+/calmodulin-dependent protein kinase (CAMK)-dependent signaling pathway, which aid dopamine efflux (Vaughan Foster, 2013). Methamphetamine increases efflux of catecholamines like norepinephrine and dopamine and prevents its uptake. This results in the increased dopamine neurotransmission in the mesolimbic pathway and central nervous system (CNS) stimulation. This CNS stimulation leads to the enhancement in the performance. Hence methamphetamine is a psychostimulant (Miller, 2011). There are many animal studies available for the increased locomotor activity in rats and animals (Hall et al., 2008; Zakharova et al., 2009; Kubota et al., 2002). In humans methamphetamine produces motor activity similar to animals, however this motor effect is evident only in acute cases and not in the chronic cases (Caligiuri Buitenhuys, 2005). Methamphetamine inhibits DAT, which is instrumental in evading dopamine form the neural synapse. In case of blocked of DAT, there is the increased dopaminergic activity in the neural synapse. With the antagonism of dopamine receptor there is the decreased dopaminergic activity and consequently reduced locomoator activity induced by amphetamine. There are different studies available for effect of dopamine receptor antagonism and its effect on the locomotor activity induced amphetamine. D2 receptor null mutant and dopamine receptor anatogonist inihibit the increased locomotor activity after the administration of amphetamine (Yun, 2014). Based on the available information, it has been postulated that amphetamine administration in the rats exhibit increased locomotor activity and this increased locomotor activity can be inhibited by administering dopamine receptor antagonist. Hence in this experiement, locomotor activity was induced in the rats and this increased locomotor activity was i nhibited by administering dopamine receptor antagonist. Discussion: In this experiment, locomotor activity of each rat was measured with Omnitech locomotor chambers. It was observed that there is the statistically significant increase in the locomotor activity in the rats after the administration of the amphetamine which is consistent with the literature results both in preclinical and clinical studies (Hall et al., 2008; Zakharova et al., 2009; Kubota et al., 2002). This increased locomotor activity is due to the methamphetamine which increases dopaminergic activity in the neural synapse and produces locomotor activity. After treatment with SCH23390, which is a dopamine 2 (D2) antagonist, there is the decrease in locomotor activity. This decrease in locomotor activity is consistent with the results of the preclinical and clinical studies (Yun, 2014). Strengths of these experiments are training or acclimatization to rats was provided to both the experimenter and experimental conditions. This training is important for getting the consistent results in behavioral studies. Animals in these experiments were not randomized equally based on the body weight or locomotion readout of the rats. If animals would have been distributed to each group with equal average body weight or average locomotion readout, that would have been given more robust treatment effect without any variability. Moreover, in this study number of animals per group were 6. If number of animals per group would have been 8-10, it would have given better results with robust statistical difference among the vehicle treated and treatment groups. Statistical significance in this study obtained is less. It can be improved by increasing the number of animals. Methamphetamine is having good oral bioavailability and oral route is one of the common routes of consumption of methamphetamine. In such scenario, if methamphetamine would have been given by oral route in this study, it could have reflected study closer to clinical scenario. SCH-23390 is specifically a D1 receptor antagonist (Derlet et al., 1990). Addiction phenomenon occurs in the D1-type medium spiny neurons of the nucleus accumbens of ventral striatum. Hence, SCH-23390 exhibits its action of locomotion inhibition in the medium spiny neurons of the ventral striatum. SCH-23390 exhibits minimal action on D2 receptor along with the major action on the D1 receptor. It has been established that there is decreased body weight, persistent depletion of striatal and cortical dopamine levels post termination of the drug administration, reduced expression of striatal and cortical tyrosine hydroxylase and DAT proteins and increased expression of glial fibrillary acidic protein in striatum and cortex, after self administration of the methamphetamine. Due to these biochemical changes, there is mental and physical retardation, dementia, seizers and addiction. Methaphetamine decreases social interaction in open field and impaired acquisition of spatial discrimination in operant chamber (White et al., 2009). Methaphetamine exhibited impaired memory acquisition and retention in the morris water maze with the help of place navigation test, probe test and retention memory test (Macuchova et al., 2013). In executive tasks in human, methamphetamine exhibited variable results after acute and chronic administration. After acute administration of methamphetamine with dose lower than abuse induction, methamphetamine exhibits improvement in memory, however after chronic administration it exhibits impairment in memory (Hart et al., 2012). References: Caligiuri, M. P., Buitenhuys, C. (2005). Do Preclinical Findings of Methamphetamine-Induced Motor Abnormalities Translate to an Observable Clinical Phenotype?. Neuropsychopharmacology, 30, 21252134. Derlet, R. W., Albertson, T. E., Rice, P. (1990). The Effect of SCH 23390 Against Toxic Doses of Cocaine, d-Amphetamine and Methamphetamine. Life Sciences. 47(9), 821827. Hall, D.A., Stanis, J.J., Avila, H. M., Gulley, J. M. (2008). A comparison of amphetamine- and methamphetamine-induced locomotor activity in rats: evidence for qualitative differences in behavior. Psychopharmacology, 195(4), 469478. Hart, C.L., Marvin, C.B., Silver, R., Smith, E.E. (2012). Is Cognitive Functioning Impaired in Methamphetamine Users? A Critical Review. Neuropsychopharmacology, 37(3), 586608. Kubota, Y., Ito, C., Sakurai, E., Watanabe, T., Ohtsu, H. (2002). Increased methamphetamine-induced locomotor activity and behavioral sensitization in histamine-deficient mice. Journal of Nurochemistry, 83(4), 837845. Macuchova, E., Nohejlova-Deykun, K., Slamberova, R. (2013). Effect of Methamphetamine on Cognitive Functions of Adult Female Rats Prenatally Exposed to the Same Drug. Physiological Research, 62(1), S89-S98. Miller, G.M. (2011). The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity. Journal of Neurochemistry, 116(2), 164176. National Ice Taskforce (NIT), Final Report (2015), Commonwealth of Australia: 1-231. Vaughan, R.A., Foster, J.D. (2013). Mechanisms of dopamine transporter regulation in normal and disease states. Trends in Pharmacological Sciences, 34(9), 489496. White, I. M., Minamoto, T., Odell, J.R., Mayhorn, J., White, W. (2009). Brief Exposure to Methamphetamine (METH) and Phencyclidine (PCP) during Late Development Leads to Long-Term Learning Deficits in Rats. Brain Research, 1266, 7286. Xie, Z., Miller, G.M. (2009). A receptor mechanism for methamphetamine action in dopamine transporter regulation in brain. Journal of Pharmacology and Experimental Therapeutics, 330 (1), 316325. Yun, J. (2014). Limonene inhibits methamphetamine-induced locomotor activity via regulation of 5-HT neuronal function and dopamine release. Phytomedicine, 21(6), 883887. Zakharova, E., Leoni, G., Kichko, I., Izenwasser, S. (2009). Differential effects of methamphetamine and cocaine on conditioned place preference and locomotor activity in adult and adolescent male rats. Behavioural Brain Research, 198(1), 4550.