lecture 6 Flashcards
what factors influence psychoactive drug taking
Perception; Learning/Reward; Changes to behavioural systems Pharmaceutical action (dopamine and serotonin) Non-pharmaceutical determinants (what you are seeing, doing, hearing)
what do we know about percpetion and drug taking (litjens et al., 2014)
Smearing effects and repetitive image effects can be studies through invoking HPPD with hallucinations
Visual hallucinations from psychedelics seem related to serotoninergic 5-HT2a
what is the relationship between food and drugs
Dopamine (Bassareo & Di Chiara 1999)
Food rewards coincide with release of dopamine
There is a learning response when food generates this dopamine signal
Impact on learning of drugs: produce reward like effects in the same way that food does in the mesolimbic system and dopamine response
what is meant by conditioned place preference (CPP) di chiaria & Imperato 1988
Drugs of abuse that humans take produce changes in rats’ sensitivity to the place that they receive the drug.
Learned preference to rooms associated with drugs
Change in dopamine signal follows this learning
Change learning about the world/ cues in environment - enhancing effect (pavlovian)
Produce a common change in signal (morphine/ amphetamine/ cocaine etc)
how is dopamine release influenced by the nature of the beahvioural association
Comparison of Self-administration (instrumental) and passive (pavlovian) administration shows that both produce dopamine responses, so learning happens in both conditions
However, the act of pressing a lever produces a stronger dopamine response than when rats simplu receive drugs
This indicates that instrumental action enhances the effect
Research suggests that people take cocaine more in external environments that generate arousal (as opposed to when they are at home)
The place individuals take recreational drugs has an impact
May interact with personal dispositions
oestrogen and cocain dependent learning (Calipari et al., 2017)
Oestrous-cycle dependent mechanism controlling increased cocaine reward in females
During oestrus, ventral tegmental area (VTA) dopamine neuron activity is enhanced and drives post translational modifications at the dopamine transporter (DAT) to increase the ability of cocaine to inhibit its function (mediated by estradiol)
Male and dioestrous and oestrous females all show preference for cocaine paired room but this is significantly stronger with oestrus females
Therefore activity-dependent changes in dopamine transporter function during oestrus leads to increased cocaine conditioned place preference
what are the major theories of compulsive drug use
Disruption of hedonic homeostasis (Koob & Le Moal, 1997; recall Siegel, 1977) Sensitization of wanting system (Robinson & Berridge, 2001) Habit learning (Everitt & Robbins, 2005) Loss of impulse control (Bechara, 2005)
what does lamb’s (1991) behavioural sensitisaiton study tell us about wanting vs liking
Reinforcing (wanting) and subjective (liking) effects of morphine determined in 5 human volunteers with histories of heroin abuse
Responding under a second order schedule of i.m injection where 100x lever presses produced a brief stimulus light (fixed ratio, FR), the 30th completion of FR100 turned the light on for 15 minutes and the participant received an i.m. injection of morphine
Once each weekday morphine or placebo was available
Morphine doses were manipulated (low, medium 3.75mg, high 7.5/15/30mg) and each dose was available for one week
Placebo did not maintain responding, 3.75mg maintained responding in ⅘ participants and higher doses (7.5, 15, 30 mg) maintained responding in all participants.
Participants did not report subject effects different from placebo for low doses of morphine, but did for the highest dose of morphine
Indicates significant dissociations between reinforcing and the subjective effects of opioids.
what did vesina (2007) show about neurochemical sensitisaiotn with drug use
Rats repeatedly exposed to amphetamine will exhibit a sensitised (enhanced) locomotor response when they encounter the drug again
In these rats, the ability of amphetamine to increase extracellular levels of DA in the forebrain is also enhanced
These effects are long lasting (locomotion: up to 1 year, DA: 3 months)
what does Alexander et al.,’s (1978 ) rat park study show about the environmental impact on drug taking
Type of environment animals are in impact the amount of drugs they will take
Morphine consumption varies depending upon housing, rather than exposure to drug
Rats consumed more morphine in isolated environments than when they were socially housed
Suggestion that positive social experience can decrease drug taking behaviour - however this is very simplistic
what is the serotonin hypothesis of nausea
Serotonin in the forebrain may be responsible for sensation of nausea
what do Limebeer et al.’s 2004 study on serotonin and nausea reveal
Investigates the effect of decreasing serotonin on gaping response, with a causal model
Administers neurotoxin (5,7-DHT) which selectively produces a selective serotonin neurochemical lesion in the dorsal and medial raphe nuclei in midbrain
Coil use an agonist which would increase serotonin
Gaping response as proxy measure for the effect of serotonin on nausea
Presented rats with LiCl saccharin solution or saline solution and tested their taste reactivity 72 hours later.
Significant reduction in gaping response (error bars overlap with administration of saline) compared to sham lesions
what do Tuerke et al.’s (2012) serotonin agonist and antagonist studies show
Intracranial ondansetron (OND, a 5HT3 antagonist)—Sac->LiCl (2 trials, 72 hr apart) 72 hr Test Sac
Taste associated with emetic drugs produces conditioned disgust reactions
Partial depletion of 5-HT in the insular cortex prevents Li-Cl induced conditioned disgust reactions
Intracranial administration of m-chlorphenbiguanide (mCPBG) enhanced the establishment of Li-Cl conditioned gaping
Dissociation found between posterior and interior IC
activation of 5-HT3 receptors in the posterior IC is important for the production of nausea-induced conditioned disgust reactions, while activation of 5-HT3 receptors in the anterior IC are involved in the production of CTA.
what are the rodent models of depression (Cryan & Holmes, 2005)
Instrumental helplessness: animals learn they cannot change their circumstances
Forced swim test
Tail suspension
Anhedonia: sense that something is rewarding
Sucrose preference
Intracranial brain stimulation
Affective bias can be induced: either positive/negative and external/internal
Maternal separation
Enriched environment
Social exposure
Unpredictable housing (Harding et al., 2004)
what does Harding et al.’s (2004) negative bias study tell us
Rats trained to press a lever during tone 1 for positive event (food) and without responding during tone 2 to avoid a negative event (loud noise)
Then exposed to either predictable (open) or unpredictable (closed) housing
In unpredictable housing 0-2 negative interventions a day
Rats exposed to non-reinforced tones that has frequencies intermediate between food and loud noise tones
Measured proportion of tones responded to by lever pressing and mean response latencies
Rats in unpredictable housing were slower to press the lever in response to the food tone and ambiguous tones close to it and responded less
Should respond to tone that resembles food tone similarly if they are optimistic
Shows pessimistic response bias can be measured in rats that are housed in unpredictable conditions
Cognitive bias can be used as an indicator of affective states in animals
Practical uses in animal welfare studies
what does stuart et al.’s affective bias study show us
Discrimination learning sessions: rats encounter two independent positive experiences: diffing in holes with food rewards
Two separate days under neutral or pharmacological/ affective state manipulation
Affective bias is quantified using a preference test where both previously rewarded substrates are presented and the rat’s choice is recorded
Significant positive affective biases following treatment with antidepressants
Significant negative affective biases following treatment with drugs associated with negative affective states
Psychosocial stress and environmental enrichment induce significant affective biases supporting the role of memory consolidation
Results suggest that cognitive affective biases could contribute to drug or stress induced mood changes in people
what were the findings of Alloy & Abramson’s (1979) human learned helplessness task
Participants were presented with one of a series of problems varying in the degree of contingency.
In each problem, participants estimated the degree of contingency between their responses (pressing or not pressing a button) and an environmental outcome (onset of a green light).
Depressed participants’ judgments of contingency were highly accurate in all 4 experiments.
Nondepressed participants overestimated the degree of contingency between their responses and outcomes
Explanation: learned helplessness and self-serving motivational bias hypotheses
what does Msetifi et al.’s, (2005) instrumental responding study show
The perception of the effectiveness of instrumental actions is influenced by depressed mood
Depressive realism: the claim that depressed people are particularly accurate in evaluating instrumentality
Action-outcome contingency judgement task found DR effects when participants were exposed to extended periods in which no actions or outcomes occurred
May result from impairment in contextual processing rather than accurate but negative expectations
Consistent with a cognitive distortion view of depression
what are SSRIs
Selective serotonin reuptake inhibitors (SSRIs) change the activity of 5-HTT such that there is an increase in activity and more reuptake of 5-HT in the presynaptic neuron
(Harmet et al., 2009)
Given different contingencies and measure action judgements
Taking drug when not needed find that it enhances action agency
Depression enhanced lack of sensitivity of environmental influence
what is tryptophan
Tryptophan:One of the essential dietary amino acids, precursor of Auxin, Niacin and Serotonin
Depletion of Tryptophan:
Lowers plasma levels of Tryptophan
Increases competition between Tryptophan and other neutral amino acids for transport across the blood brain barrier
Chase et al. (2011) tested participants on and off a tryptophan depletion drink and looked for decreased contingency and context processing
