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  • 1
    Electronic Resource
    Electronic Resource
    Amygdala and hippocampus control dissociable aspects of drug-associated conditioned rewards (1997)
    Springer
    Psychopharmacology 131 (1997), S. 187-195 
    Details
    ISSN: 1432-2072
    Keywords: Key words Intracranial self-administration ; Conditioned reward ; d-Amphetamine ; CNQX ; Nucleus accumbens ; Ventral subiculum ; Basolateral area of the amygdala
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Limbic innervation of the nucleus accumbens via the ventral subiculum/hippocampus and basolateral area of the amygdala has been shown to determine dissociable aspects of behaviour controlled by stimuli associated with natural rewards. However, the respective contributions of the ventral subiculum and amygdala to behaviour governed by drug-associated stimuli remain to be determined. Experiments consisted of two phases: drug-stimulus training, and subsequent stimulus-only testing. Initial training sessions were of two alternating forms. During drug sessions, responding upon one lever resulted in an infusion of 1 μg d-amphetamine into the nucleus accumbens, whilst during saline sessions d-amphetamine was replaced with saline. Each infusion (drug or saline) was preceded with either a light, or tone. Responding upon a control lever had no programmed consequences. Following training, the levers were retracted, and instead two novel vertical bars were extended from the chamber ceiling. Movement of one bar produced the drug-associated stimulus, whilst the alternative bar produced the saline-associated stimulus. Infusions of the AMPA receptor antagonist CNQX into the ventral subiculum or basolateral area of the amygdala (0, 0.2, 2.0 nmol) were made immediately before the start of each session. Intra-basolateral area of the amygdala CNQX reduced responding upon the drug-associated stimulus bar, but at the same time increased responding upon the saline-associated stimulus bar. By contrast, intra-ventral subiculum CNQX reduced drug-associated stimulus responding selectively. Neither manipulation affected levels of activity within the operant chamber extraneous to the bar-pushing response. Hence, the basolateral area of the amygdala appeared to have determined the degree of discriminative control exerted over behaviour by the drug-associated stimulus, whilst the ventral subiculum is suggested to have determined the efficacy of the conditioned reward.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050283
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  • 2
    Electronic Resource
    Electronic Resource
    Enhanced conditioned inhibition following repeated pretreatment with d-amphetamine (1999)
    Springer
    Psychopharmacology 142 (1999), S. 120-131 
    Details
    ISSN: 1432-2072
    Keywords: Key words Sensitisation ; d-Amphetamine ; Conditioned inhibition ; Amygdala ; Nucleus accumbens ; Reward ; Conditioning
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have shown that prior repeated exposure to d-amphetamine facilitates appetitive Pavlovian conditioning. However, animals sensitised in this manner also show elevated levels of stimulated activity. To investigate whether enhanced conditioning was dependent upon increased activity, a conditioned inhibition task was employed in the present study. Rats received d-amphetamine (2 mg/kg, IP) or vehicle once per day for 7 days. After a 7-day drug-free period, an activity assay confirmed that repeated d-amphetamine treatment markedly elevated the locomotor response to a subsequent challenge with 0.5 mg/kg d-amphetamine. Conditioning began 6 days later. In phase 1, stimulus A+ (light or tone) immediately preceded sucrose availability (excitatory conditioning). In phase 2, sucrose again was presented after A+ alone, but not after presentation of a compound of A+ with a second stimulus (AB−). Sensitisation enhanced the acquisition of conditioned approach behaviour to the excitatory stimulus A+ in phase 1. Furthermore, acquisition of conditioned inhibition to the stimulus compound, AB−, was also facilitated. Thus, sensitised rats showed reduced levels of responding to the stimulus compound far sooner than controls. Finally, a retardation test was carried out in stage 3, in which the inhibitory stimulus B- was paired alone with sucrose reward. Sensitised rats initially showed retarded acquisition of excitatory conditioned responding relative to controls, suggesting that B possessed stronger inhibitory associations in these animals. However, sensitised animals again exhibited higher levels of responding in later sessions, consistent with the enhanced excitatory conditioning shown in phase 1. These findings suggest that prior repeated d-amphetamine enhanced the acquisition of inhibitory and excitatory Pavlovian associations; a propensity not readily attributable to stimulated locomotor hyperactivity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050870
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  • 3
    Electronic Resource
    Electronic Resource
    Repeated d-amphetamine enhances stimulated mesoamygdaloid dopamine transmission (1997)
    Springer
    Psychopharmacology 132 (1997), S. 247-254 
    Details
    ISSN: 1432-2072
    Keywords: Key words Dopamine ; Sensitisation ; Microdialysis ; Amygdala ; Nucleus accumbens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The mesoaccumbens dopamine pathway exhibits an enhanced dopaminergic response to a challenge injection of d-amphetamine or cocaine after repeated intermittent exposure to that drug. Much research has focused on the potential role of this sensitised response in the enhanced propensity of drug-associated stimuli to elicit relapse. However, the amygdala is acknowledged to play a critical role in stimulus-reward learning, and recent work suggests that the mesoamygdaloid dopamine pathway exerts a significant influence upon amygdala function. In the present study, rats were administered d-amphetamine (1 mg/kg, IP) or vehicle once per day, for 14 days. After 11 untreated days, a locomotor assay showed that prior repeated administration of d-amphetamine led to a markedly enhanced locomotor response to 0.5 mg/kg d-amphetamine. There was no effect of d-amphetamine pretreatment upon the response to a novel environment, or to injection with vehicle. Following a total of 14 days in the home cage, subjects were implanted with microdialysis probes within the amygdala, and for comparison also within the nucleus accumbens. Baseline and d-amphetamine-stimulated (0.5 mg/kg) levels of extracellular dopamine were assessed for each brain region. Results showed that baseline levels of dopamine were very similar in sensitised and control animals. By contrast, prior treatment with d-amphetamine enhanced dopamine overflow in response to a challenge with d-amphetamine both in the nucleus accumbens and amygdala. These results indicate that changes in the pattern of dopamine transmission both in the nucleus accumbens, and the amygdala, accompany the behavioural sensitisation observed after repeated exposure to d-amphetamine. Hence, an enhanced propensity of drug-associated stimuli to elicit relapse may not depend solely upon changes relating to the mesoaccumbens dopamine projection.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050342
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  • 4
    Electronic Resource
    Electronic Resource
    Cross-sensitisation with d-amphetamine following repeated intra-perifornical sulpiride infusions (1997)
    Springer
    Psychopharmacology 133 (1997), S. 179-187 
    Details
    ISSN: 1432-2072
    Keywords: Key words Perifornical region of the lateral hypothalamus ; Sulpiride ; Sensitisation ; Conditioning ; Mesoaccumbens dopamine projection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Infusions of the dopamine D2/D3 receptor antagonist sulpiride within the perifornical region of the lateral hypothalamus have been reported to increase locomotor activity. The current investigation examined the effect of repeated lateral hypothalamic sulpiride infusions. In experiment 1a, rats were placed repeatedly in an activity chamber either prior to, or following an infusion of 10 μg sulpiride or vehicle. Repeated infusions of sulpiride prior to, but not following exposure to the activity chamber increased locomotor activity during subsequent sessions. In experiment 1b, repeated pretreatment with intra-perifornical sulpiride prior to placement within the activity chamber was found to engender a significant increase in conditioned activity when placed subsequently within the same chamber drug-free. Alternatively, pretreatment with sulpiride in the home cage was found subsequently to engender a significant increase in locomotor activity during a test session with intra-perifornical sulpiride. In experiment 2, repeated pretreatment with intra-perifornical sulpiride significantly increased the locomotor response to a subsequent systemic challenge with d-amphetamine. Animals pretreated in the home cage exhibited a moderate increase in activity over vehicle controls, while animals repeatedly pretreated immediately prior to placement in the activity chamber exhibited the largest response subsequently to d-amphetamine of any group. Experiment 3 showed that repeated sulpiride infusions either 1 mm anterior or 1mm posterior to the perifornical region were without effect upon locomotor activity. These data are suggested to reflect an indirect action of intra-perifornical sulpiride upon the mesoaccumbens dopamine projection, via the level of the ventral tegmental area. Precise neural mechanisms are under current investigation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050389
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  • 5
    Electronic Resource
    Electronic Resource
    Interactions between intra-perifornical region sulpiride and intra-ventral tegmental area AP5 on measures of locomotor activity and conditioned place preference (1998)
    Springer
    Psychopharmacology 136 (1998), S. 105-113 
    Details
    ISSN: 1432-2072
    Keywords: Key words Perifornical region of the lateral hypothalamus ; Ventral tegmental area ; Dopamine ; Activity ; Conditioned place preference ; Sulpiride ; AP5
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Infusions of sulpiride, a dopamine D2/D3 receptor antagonist within the perifornical region of the lateral hypothalamus have been shown previously to exhibit a behavioural profile generally attributed specifically to activation of the mesoaccumbens dopamine projection. Experiment 1 confirmed previous work showing that repeated homecage pretreatment with sulpiride (5 μg) in the perifornical region of the lateral hypothalamus resulted subsequently in an enhanced locomotor response to a d-amphetamine challenge. Experiment 2 examined the possibility that the observed behavioural changes were due to stimulation of the mesoaccumbens dopamine projection via the ventral tegmental area. Thus, repeated intra-perifornical infusions with sulpiride were without effect initially, but resulted in a gradual increase in locomotor activity during subsequent sessions. Intra-ventral tegmental area infusions of the NMDA receptor antagonist AP5 (0.3, 1.0 nmol) were without intrinsic effect upon locomotor activity at any time. However, AP5 blocked the ability of repeated sulpiride infusions to increase locomotor activity, and the ability of intra-perifornical sulpiride to support the acquisition of a conditioned place preference. AP5-sulpiride co-infusions also increased locomotor activity in a non-incremental manner. These data suggest there to be a functionally significant projection from the perifornical region of the lateral hypothalamus to the ventral tegmental area in the control over locomotor activity and rewarded behaviour.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050545
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  • 6
    Electronic Resource
    Electronic Resource
    Post-session sulpiride infusions within the perifornical region of the lateral hypothalamus enhance consolidation of associative learning (1998)
    Springer
    Psychopharmacology 140 (1998), S. 354-364 
    Details
    ISSN: 1432-2072
    Keywords: Key words Perifornical region of the lateral hypothalamus ; Amygdala ; Pavlovian conditioning ; Sulpiride ; Dopamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Whilst neurons within the lateral hypothalamus are well known to be responsive to the presentation of previously learned associative stimuli, the consolidation of a Pavlovian association is thought to depend in large part upon other brain regions, including the amygdala. The present study addressed this assumption directly, by examining the effect of post-session infusions of sulpiride within the lateral hypothalamus upon the acquisition of a conditioned approach response in an appetitive differential conditioning task. Subjects were exposed to an initially neutral stimulus (CS+), which immediately preceded the availability of a 10% sucrose reward (US). A second, control stimulus (CS−) was also presented, but never in close temporal proximity to the US. The number and duration of alcove approaches were recorded. Immediately following each training session, subjects were infused bilaterally with sulpiride (0, 0.5, 5 μg) in the vicinity of the perifornical region of the lateral hypothalamus. Sulpiride dose-dependently enhanced the rate of acquisition of a conditioned approach response to presentation of the CS+, but was without affect upon approach behaviour during CS− or US presentations. Thus, 0.5 μg sulpiride facilitated at an early stage (session 2 onwards) the number of alcove approaches to the CS+, while 5 μg sulpiride enhanced to a greater extent the duration of conditioned approach, particularly during later sessions. A subsequent locomotor test using 0.5 mg/kg d-amphetamine indicated that repeated infusions of the higher dose sulpiride (5 μg), but not the lower dose (0.5 μg), resulted in behavioural sensitisation to administration of the psychomotor stimulant. Acquisition of a novel conditioned instrumental response was not affected by previous exposure to sulpiride. These data suggest that dopamine-sensitive neurons within the lateral hypothalamus may play a significant role in the acquisition of appetitive Pavlovian associations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050776
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  • 7
    Electronic Resource
    Electronic Resource
    The biological, social and clinical bases of drug addiction: commentary and debate (1996)
    Springer
    Psychopharmacology 125 (1996), S. 285-345 
    Details
    ISSN: 1432-2072
    Keywords: Dependence ; Addiction ; Drug abuse ; Craving ; Relapse ; Tolerance ; Sensitization ; Withdrawal ; Opponent process theories ; Subjective ; Discriminative effects ; Reinforcement ; Habit ; Neural systems ; Psychomotor stimulants ; Amphetamine ; Cocaine ; Oppiates ; Alcohol ; Nicotine ; Hallucinogens ; Amygdala ; Stratum ; Nucleus accumbens ; Dopamine ; 5-HT ; Cerebral cortex ; Functional neuroimaging ; PET ; Transcription factors ; Behavioural genetics ; Strain-dependent effects ; Quantitative trait loci ; Individual differences ; Risk factors ; Personality and dependence ; Biological markers of dependence ; Co-morbidity ; Schizophrenia ; Depression ; Pharmacological treatment for dependence ; Psychosocial treatment of dependence ; Sociology of dependence ; Epidemiology of dependence ; Animal models of dependence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This article summarizes the main discussions at a meeting on the biological, social and clinical bases of drug addiction focused on contemporary topics in drug dependence. Four main domains are surveyed, reflecting the structure of the meeting: psychological and pharmacological factors; neurobiological substrates; risk factors (including a consideration of vulnerability from an environmental and genetic perspective); and clinical treatment. Among the topics discussed were tolerance, sensitization, withdrawal, craving and relapse; mechanisms of reinforcing actions of drugs at the behavioural, cognitive and neural levels; the role of subjective factors in drug dependence; approaches to the behavioural and molecular genetics of drug dependence; the use of functional neuroimaging; pharmaceutical and psychosocial strategies for treatment; epidemiological and sociological aspects of drug dependence. The survey takes into account the considerable disagreements and controversies arising from the discussions, but also reaches a degree of consensus in certain areas.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02246016
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  • 8
    Electronic Resource
    Electronic Resource
    Effects of intra-amygdala R(+) 7-OH-DPAT on intra-accumbens d-amphetamine-associated learning I. Pavlovian conditioning (1998)
    Springer
    Psychopharmacology 140 (1998), S. 300-309 
    Details
    ISSN: 1432-2072
    Keywords: Key words Dopamine ; Amygdala ; Nucleus accumbens ; Pavlovian conditioning ; R(+) 7-OH-DPAT ; d-Amphetamine ; D3 receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have previously obtained evidence that the mesoamygdaloid dopamine projection modulates the acquisition of a conditioned response (CR) elicited by presentation of a conditioned stimulus (CS) predicting the availability of a natural (sucrose) reward. This property was found to be dependent upon D3, but not D1 or D2, dopamine receptor activation. The aim of the present study was to determine whether the mesoamygdaloid dopamine projection is similarly involved in the acquisition of a drug-associated CR. Thus, two groups of rats with guide cannulae aimed at the nucleus accumbens and amygdala were trained using a Pavlovian conditioning procedure in which an initially neutral CS was paired with a computer-controlled, bilateral intra-accumbens infusion of d-amphetamine (the unconditioned stimulus; US). Conditioning sessions were conducted in standard operant chambers, with each session consisting of a single CS-US trial. For one group of rats, CS presentation was positively correlated with the drug US (Paired group), while for the second group CS and US presentations were negatively correlated (Unpaired group). During training, locomotor activity was recorded and was utilised as the measure both of the unconditioned (UR) and conditioned response (CR). A within-subjects design was utilised to investigate the effect of post-session bilateral intra-amygdala administration of R(+) 7-OH-DPAT on the development of the drug-associated CR. Hence, both Paired and Unpaired groups were exposed to two different CSs which were presented on alternate sessions. Post-session bilateral intra-amygdala administration of R(+) 7-OH-DPAT (10 nmol) followed sessions in which one CS was presented, while intra-amygdala vehicle followed sessions in which the alternate CS was presented. The development of a CR occurred only in the presence of a CS that had been positively correlated with presentation of the drug US. Post-session, intra-amygdala administration of R(+) 7-OH-DPAT enhanced the acquisition of this CR. However, R(+) 7-OH-DPAT was without effect upon the unconditioned response to intra-accumbens d-amphetamine. Our previous data indicate a comparable effect of R(+) 7-OH-DPAT on conditioning to a CS associated with a non-drug, natural reward. Therefore, taken together, these findings suggest that D3 dopamine receptors within the amygdala modulate specifically the acquisition of Pavlovian conditioned responses, regardless of whether drug or natural rewards constitute the US.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050771
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