Dr Juan J. Canales
Phone +64 3 364 2987 (Ext. 45644)
Internal Phone 45644
Lab ext 7303
Department of Psychology
University of Canterbury
Private Bag 4800
Awards & Distinctions
2008 – Visiting Professor, Catholic University of Valencia, Spain
2006 – Institute Investigator (with tenure), University of Valencia, Spain
2004 – I3 National Certification of Excellence in Research, Spain
2001 - Investigator Award of the Ramón y Cajal Program, Ministry of Science and Technology, Spain
2000 – Repatriation Fellowship Award of the Ministry of Science and Technology, Spain
1999 – FVIB Postdoctoral Award, Spain
1998 - Special Postdoctoral Fellowship Award of the National Parkinson Foundation, USA
1997 – Postdoctoral Fellowship Award of the Theodore & Vada Stanley Foundation, USA
1994 - Scholarship Award of the Medical Research Council, United Kingdom
- PSYC212 - Foundations of Behavioural Neuroscience - Course Coordinator
- PSYC333 – Biological Psychology
- PSYC463 – Neuroscience of Addictive Behaviour - Course Coordinator
Statement of research
I aim to understand the biological and psychological substrates of addictive behaviour and how these overlap with the brain processes that mediate learning, memory, motivation and emotion. I investigate the changes that drugs produce in the brain and the way in which drugs affect perception and cognition. One of my main priorities is the discovery and evaluation of novel, more efficacious medications to treat patients suffering from addictive disorders. I welcome enquiries from motivated students willing to collaborate with my team or to join my lab to pursue a UC Master or Ph.D. degree, as well as from talented postdoctoral associates wishing to continue their research career in New Zealand.
Research opportunities in the Canales lab
I am currently accepting Master students, Ph.D. students and postdoctoral associates. I am not able to provide stipends or salaries but I will support applications from excellent researchers to national and international funding agencies. Check the links below for further information.
New Zealand International Doctoral Research Scholarships
The New Zealand International Doctoral Research Scholarships (NZIDRS) are funded by the New Zealand Government. Applications will be accepted from late May until 5pm (NZ time) on Friday the 15th of July 2011.
UC International Doctoral Scholarships
These Doctoral Scholarships are tenable by international students for study towards the degree of Doctor of Philosophy at the University of Canterbury. Closing date 15th of May.
UC Doctoral Scholarships
University of Canterbury Doctoral Scholarships are tenable for study towards the degree of Doctor of Philosophy at the University of Canterbury. Closing date 15th of May.
UC Master’s Scholarships
University of Canterbury Master's Scholarships are tenable for study towards a Master's degree at the University of Canterbury. Closing date 15th of May.
UC College of Science Doctoral Scholarships
These scholarships are tenable for study towards the degree of Doctor of Philosophy at the University of Canterbury. Closing date 15th of October.
Te Rau Matatini Master’s & Ph.D. scholarships
Undergraduate, postgraduate and (often) postdoctoral scholarships to work in the problem gambling sector. Closing date January each year.
Pacific Health Research Postgraduate Award – Master’s & Ph.D. scholarships
This Scholarship offers personal support for outstanding graduate students for three years. The research programme is generally aimed at a higher degree (a PhD or Doctorate) in any discipline related to improving the health of Pacific people. Applicants should be a New Zealand citizen or permanent resident. Check website for closing dates.
Pacific Health Research Postdoctoral Fellowships
This Fellowship provides support for outstanding graduates who have recently completed a degree at doctoral level and who propose to conduct research in any discipline related to improving the health of Pacific people. Applicants should be a New Zealand citizen or permanent resident. Check website for closing dates.
International Human Frontier Science Program – Postdoctoral research
The Program's major objectives are to promote interdisciplinary and intercontinental collaboration and mobility. New Zealand is a supporting member of this Program. Check website for closing dates.
Commonwealth Scholarship and Fellowship Plan (CSFP)
The Commonwealth Scholarship and Fellowship Plan (CSFP) is an international programme under which member governments offer scholarships and fellowships to citizens of other Commonwealth countries. Awards include postgraduate Scholarships – at both Master’s and doctoral level –, Post-Doctoral Fellowships, undergraduate exchange, and short Professional Fellowships. Check with Your National Agency for closing dates (http//www.csfp-online.org/agencies.html).
Lines of research
Neurobiology of Drug Addiction
Drug addiction is a brain disease characterized by recurrent, compulsive-like behaviour aimed at procuring and taking drugs, loss of control over intake and strong propensity to relapse, even after prolonged periods of abstinence. The disease probably develops progressively and the resilience and persistence of the behaviours associated with it suggests that long-lasting modifications occur in the brain of individuals suffering from drug addiction.
Most of my past and current work focuses on psychomotor stimulant drugs, such as cocaine and methamphetamine. We know that most abused drugs activate the dopamine projection to the nucleus accumbens, in the ventral striatum, a system that has evolved to facilitate learning about motivationally salient stimuli, often referred to as natural rewards, including food, sex and social interaction. It is likely that the initial learning about the rewarding and reinforcing effects of drugs is mediated, at least partially, by this pathway, as is learning about those important natural rewards. The striatum is organized as a gradient which sub serves goal-directed, motivationally important behaviours, represented ventrally, and habit-like behaviours, represented dorsolaterally. With repeated exposure, drugs progressively impact on the dorsolateral striatum (DST). These effects may be relevant to the habit-forming actions of drugs of abuse. Previous animal studies have shown that neurons of the DST encode habit-like associations after extended procedural learning, whereas neuronal inactivation of the same region disrupts habit-like drug-seeking actions. Yet, the effects of drugs on the DST are compartmentally-specific and therefore a deeper level of analysis is required. Chronic exposure to stimulant drugs induces disorganising effects on the pattern of activation of the neurochemical compartments of the DST (so-called striosomes and matrix). The implications of such a specific form of plasticity to habit learning are presently unknown and I aim to understand how it contributes to drug addiction.
From a systems-level perspective, it is plausible that the habit-forming actions of drugs also result from the dynamic engagement of a circuitry that expands beyond the DST including at least the prefrontal cortex (PFC) and the hippocampus (HIP). Lesions of the PFC regulate response-outcome and habit learning and some PFC manipulations mimic the effects of chronic stimulant exposure on striatal activity. Further, the impairing actions of drugs on hippocampal function may be one of the mechanisms by which drugs seize the habit learning system. Drugs and stressors disrupt adult hippocampal neurogenesis, which in turn may facilitate habit-learning. Some interactions of the PFC and HIP with striatal-based memory systems have been previously studied, but not while drug-related habits are being formed. One of my objectives is to study these interactions.
Experimental Therapeutics for Stimulant Addiction
TRACE AMINE ASSOCIATED RECEPTORS. Trace amines (TAs), including -phenylethylamine, p-tyramine, octopamine and tryptamine, represent a group of endogenous amines intimately related to the classical neurotransmitters. For decades, TAs have been referred to as “false neurotransmitters” because their effects on the brain’s neurophysiological activity were believed to be indirect. At the turn of the 21st century, however, investigations discovered TAAR1, a receptor subtype phylogenetically conserved in the brain of mammals, including humans. This receptor is found throughout the limbic and monoaminergic systems, encompassing the ventral tegmental area/substantia nigra and dorsal raphe nucleus, regions that contain the DA- and 5-HT-producing neurons, respectively. There is evidence of functional regulation of dopamine transmission by TAAR1, suggesting that this novel receptor could modulate to the long-lasting pathophysiological neuroadaptations produced by psychomotor stimulants. Moreoer, several psychoactive substances, including amphetamine, methamphetamine, MDMA (3,4-methylenedioxymethamphetamine), and lysergic acid diethylamide are themselves agonists of TAAR1. In collaboration with international laboratories, our research aims to investigate the therapeutic potential of TAAR1-based medication in drug addiction and other mental disorders.
ATYPICAL DOPAMINE UPTAKE INHIBITORS. Molecular models of dopamine transporter (DAT) binding have demonstrated that dopamine, cocaine and amphetamine binding sites extensively overlap, complicating the design of cocaine or amphetamine antagonists which do not themselves block dopamine uptake. Evidence based on structure-relationship studies showed that various classes of DAT ligands differ fundamentally in pharmacokinetic/dynamic and behavioural properties. Many of such compounds lack strong cocaine-like behavioural effects in animal models of addiction. Moreover, differences in functional activity are not predicted by the binding affinity of these compounds in vitro and their functional potency at the DAT. In addition, molecular data suggested that differential modes of interaction with the DAT lead to specific conformational alterations of the transporter, partially explaining differences in the cocaine-like behavioural effects of DAT inhibitors. Therefore, provided that the relationship among chemical structure, binding profile at the DAT and behavioural activity is non-linear, the design of compounds with DAT activity with potential therapeutic applications is theoretically feasible.
Benztropine analog compounds are potent dopamine uptake inhibitors with pharmacological and functional characteristics that differ substantially from classical stimulants, such as cocaine. These agents have strong affinity for the DAT and potently inhibit dopamine uptake. Further, benztropine analogs display rates of DAT occupancy slower than that of cocaine and produce increases in extracellular dopamine levels over prolonged periods of time, by contrast to the sharp and transient elevations produced by cocaine. These features complement their weak or limited capacity to induce cocaine-like behaviors, such as locomotor stimulation and conditioned place preference (CPP), and support the claim that they might offer a lead for the design of efficacious replacement medications for cocaine addiction. My research is aimed at evaluating novel DAT uptake inhibitors in animal models of stimulant addiction.
Some of my previous research has shown that drugs, including psychomotor stimulants and hallucinogenic compounds, such as cocaine and ecstasy, as well as adverse environmental situations, such as chronic stress, can negatively affect hippocampal neurogenesis. Neurogenesis in the adult brain is a dynamic self-renewal process that involves proliferation, migration, differentiation and functional integration of new cells into either the olfactory bulb or the granular layer of the hippocampal dentate gyrus (DG). Newly generated cells can be labeled and observed under the microscope (see figure). The finding that most addictive drugs impair neurogenesis in the adult hippocampus has opened new avenues for exploring the neurobiological basis of drug addiction. However, major gaps remain in our understanding of the relationship between drug addiction and the effects that psychoactive drugs produce on adult-generated granule neurons. One of my objectives is to understand this relationship and, more generally, delineate the contribution of adult hippocampal neurogenesis to learning and memory function.
The evidence implicating the hippocampus in addictive behaviours is substantial. The neuronal pathways and the intracellular events that mediate memory consolidation converge with those mediating drug-induced neuroplasticity. Hippocampal neurogenesis might be essential for efficient cognitive processing by the DG and by the hippocampal formation by extension. One way by which impaired neurogenesis could contribute to addiction would be by disrupting associative learning, by promoting the generalization of associations between drug experiences and stimuli, both internal and external, and by increasing susceptibility to relapse. Abused drugs also activate central stress circuits. Experimental evidence supports a role for adult neurogenesis in stress, depression and affective disorders, which are major driving forces in addiction. Abnormal neurogenesis in the adult hippocampus could bring about affective and motivational instability and sensitize neural pathways to drug-induced reward. I believe that our investigations along these pathways could significantly increase our understanding of the processes involved in drug dependence and addiction.
Editor-in-chief, Journal of Behavioral and Brain Science
Member of the Advisory Editorial Board, Current Psychopharmacology
Member of the Editorial Board, World Journal of Psychiatry
Member of the Editorial Board, International Journal of Brain and Cognitive Sciences
Member of the International Editorial Board, Neural Regeneration Research
Member of the Editorial Board, World Journal of Neurology
Issue Editor, Pharmaceuticals –Drug Abuse Targets
Editor, Drug Treatment Methods, Nova Publishers, NY