Pleasure, Psychoactives and a Basement...

This is a post I've been meaning to write for quite a while, but other exciting biological concepts got in the way. Story of this blog. The title is perhaps misleading, as it implies some kind of lugubrious activity, however the topic at hand is rather removed from such criminality, at least I hope. The lecture was titled; Pleasure, Novel Psychoactives  and the Brain's Basement (see, I wasn't lying about the basement) and was lead by Professor Gaetano Di Chiara of the University of Cagliari's Pharmacology department. The main body of the lecture revolved around the brain's response to psychoactive drugs, and the various experimental methods used to investigate the mechanisms behind the response. Professor Di Chiara was clearly passionate about his field of study, and so he went through the slides of the presentation at an astounding rate. This, combined with his somewhat broken English lead to my notes becoming rather scant at times, but despite this I would like to share what I was able to glean. Firstly, the definition of pleasure used by the Professor and his team; incentive to seek and accept biological incentives (food rewards for example). There are 2 distinctions of pleasure; Appetitive, which is preparatory and so comes from learned stimuli, and Consummatory, which is caused by proximal stimuli, and is unconditioned. The neurotransmitter Dopamine is widely believed to be responsible for the pleasure response of the brain, and is therefore connected to rewarding stimuli, which often aid in the survival of a species (feeding, reproduction etc). Addictive drugs also trigger dopamine release, as when a micro-dialysis tube is used to measure neurotransmission in the ventral striatum of the brain, psychoactive drugs produce a lasting spike in dopamine levels.  These ventral areas, around the amygdala of the brain, are phylogenetically the older areas of the mammalian brain, and are therefore referred to as the brain basement (just to clarify the lecture title). One fact that is, according to the lecture, contentious within the scientific community, or was contentious about 10 years ago, when most of this research was conducted, but also the last time Professor Di Chiara kept up with developments in this area of study (burn) (He referred to the archistriatum of the brain, which only exist in birds and are now called the Arcopallium; it's homologus to the amygdala im mammals essentially) is whether the biological function of dopamine is purely pleasure, or whether it has a motivatory function in survival of organisms. Rats are often the subjects of addiction experiments, and the Master/Yolked experimental paradigms are no different. The 'Master' rats were in a set-up which allowed them to actively expose themselves to the drug heroin, whereas the 'Yolked' (not quite sure about that nomenclature there) rats were passively being administered the drug. It was observed that Master rats experienced a greater dopamine output  in the shell of the nucleus accumbens (part of the ventral striatum), which is involved in the cognitive processing of wanting as well as reward and reinforcement effects. On the other hand the Yolked rats' response non-contingent drug exposure (I hope that's a thing) saw a a smaller increase in dopamine output in the core of the nucleus accumbens, dealing with new motor programs which facilitate the acquisition of a given reward in the future. This suggests that the master rats experienced a heightened euphoria on drug exposure, but why is this? I hear you mumble sleepily... I'm so glad you asked. The fact that the master rat group were self administering the drug was the key, as they were able to predict and therefore better cope with the side effects of the drug, something the passively drugged yolked rats were unable to do, thus prolonging the heroin high. The master rats would eventually have the conditioned stimulus of administering the drug completely replace the primary stimulus of the heroin itself. The drug essentially triggers no dopamine release, and so the IV self-administration becomes the main source, as the user has habituated to the drug. By extension of this paradigm researchers were able to link drugs of abuse with increased extracellular dopamine secretion in the accumbens shell particularly, clearly displaying dopamine's ability to promote expression of incentive-based motivation, in a Pavlovian manner. In my mind I have ended the debate; dopamine is a biological motivation tool, which can all too easily lead to dependance on unsavoury activities to achieve a pleasure sensation. So please, put the needle down...