Tribute to: Self-administered nicotine activates the mesolimbic dopamine system through the ventral tegmental area [William Corrigall, Kathleen Coen and Laurel Adamson, Brain Res. 653 (1994) 278-284].

In this paper, Dr. Corrigall and collaborators described elegant experiments designed to elucidate the neurobiology of nicotine reinforcement. The nicotinic receptor antagonist dihydro-β-erythroidine (DHβE) was infused in the ventral tegmental area (VTA) or nucleus accumbens (NAC) of rats trained to self-administer nicotine intravenously.

Teneurin C-terminal associated peptide (TCAP)-1 modulates dendritic morphology in hippocampal neurons and decreases anxiety-like behaviors in rats.

Teneurin C-terminal associated peptide (TCAP)-1 is a member of a novel family of neuropeptides that has been highly conserved throughout evolution. TCAP-1 is expressed in the limbic system in areas such as the hippocampus and amygdala. In vitro, TCAP-1 increases cytoskeletal proteins in immortalized neurons and modulates neurite outgrowth in cultured primary hippocampal neurons.

Teneurin C-terminal associated peptide (TCAP)-1 attenuates corticotropin-releasing factor (CRF)-induced c-Fos expression in the limbic system and modulates anxiety behavior in male Wistar rats.

The teneurin C-terminal associated peptides (TCAPs) are a novel family of four endogenous peptides that have previously shown bioactive properties both in vitro and in vivo. Previously we have shown that repeated intracerebral injections of synthetic TCAP-1 modulate anxiety-like behaviors in three tests of anxiety, although the neural substrates responsible for these effects were previously unknown. In the current study, we examined both c-Fos induction and behavioral responses in the elevated plus maze and open field tests after a single intracerebroventricular dose of TCAP-1 followed by an intracerebroventricular injection of CRF in male Wistar rats.

Repeated intracerebral teneurin C-terminal associated peptide (TCAP)-1 injections produce enduring changes in behavioral responses to corticotropin-releasing factor (CRF) in rat models of anxiety.

The teneurin C-terminal associated peptides (TCAP) are a recently discovered family of peptides encoded by a bioactive neuropeptide-like gene sequence found at the carboxy terminus of the teneurin transmembrane proteins. TCAP is structurally related to the corticotropin-releasing factor (CRF) family of peptides. Synthetic TCAP-3 and TCAP-1 are active in vitro in stimulating cAMP and proliferation in neuronal lines.

Corticotropin-releasing factor (CRF)-induced behaviors are modulated by intravenous administration of teneurin C-terminal associated peptide-1 (TCAP-1).

The teneurin C-terminal associated peptides (TCAP) are a recently discovered family of bioactive peptides that can attenuate aspects of the behavioral stress responses of rats. Because TCAP has some structural similarity to the corticotropin-releasing factor (CRF) family of peptides, and modulates elements of the stress response, TCAP may act to modulate CRF actions in vivo. This hypothesis was tested by investigating anxiety-related behaviors in male rats following repeated intravenous (IV) TCAP-1 administration with either an acute intracerebroventricular (ICV) or IV CRF challenge.

Individual differences in elevated plus-maze exploration predicted progressive-ratio cocaine self-administration break points in Wistar rats.

Rationale: There are considerable individual differences in vulnerability to drug addiction, but the mechanisms underlying such differences are poorly understood. Cocaine has potent reinforcing effects that support operant responding. However, cocaine also elicits aversive reactions and produces an approach-avoidance conflict in rats.

Effects of central neurokinin-1 receptor antagonism on cocaine- and opiate-induced locomotor activity and self-administration behaviour in rats.

The neuropeptide substance P (SP) and its preferred receptor, the neurokinin-1 (NK-1) receptor, have been implicated in some of the reward-related behavioural effects of abused drugs, including psychostimulants and opiates. The first objective of the present series of experiments was to assess the role of the NK-1 receptor in two reward-related behavioural effects of cocaine: locomotor activity and self-administration. In tests for locomotor activity, rats were given intracerebroventricular (ICV) infusions of the selective NK-1 receptor antagonist, GR82334 (0, 10, 50 pmol), prior to systemic injections of cocaine.

Activation of central neurokinin-1 receptors induces reinstatement of cocaine-seeking behavior.

A number of neurochemical systems have been implicated in mediating relapse to drug-seeking behavior. Substance P (SP) is a neuropeptide that interacts with some of these systems, suggesting a possible role for SP and its preferred receptor, the neurokinin-1 (NK-1) receptor, in the mediation of relapse. In this study, we examined whether selective activation of NK-1 receptors induces reinstatement of cocaine-seeking behavior, and whether endogenous activity at these receptors is involved in mediating cocaine-induced reinstatement.

Infusion of the substance P analogue, DiMe-C7, into the ventral tegmental area induces reinstatement of cocaine-seeking behaviour in rats.

Rationale: The mesocorticolimbic dopamine (DA) system is critically involved in mediating reinstatement of drug-seeking behaviour. Substance P (SP) is a neuropeptide that significantly interacts with the mesocorticolimbic system, therefore suggesting a possible role for the SP system in the mediation of relapse.

Objectives: This study examined the effects of injections of the SP analogue, DiMe-C7, into the ventral tegmental area (VTA) on reinstatement of cocaine-seeking behaviour, as well as on locomotor activity in rats.

Cholecystokinin modulation of locomotor behavior in rats is sensitized by chronic amphetamine and chronic restraint stress exposure.

DA release in the nucleus accumbens (NAcc) is a critical substrate mediating locomotor behavior. Cholecystokinin (CCK) is co-localized with dopamine (DA) in up to 90% of mesolimbic DA neurons. We have previously shown that while CCKA receptor antagonists generally do not affect locomotor behaviors, systemic administration of a CCKA receptor antagonist attenuates amphetamine (AMPH)-induced locomotion in animals previously treated chronically with AMPH, suggesting that chronic stimulant pretreatment may sensitize CCK systems.

Cholecystokinin receptor subtypes: role in the modulation of anxiety-related and reward-related behaviours in animal models.

Cholecystokinin (CCK) is an abundant and widely distributed neuropeptide that plays a modulatory role in a variety of behaviours. This paper focuses on the role of CCK in modulating anxiety-related and reward-related behaviours in key brain regions of the amygdala and mesolimbic dopamine system, respectively. The role of CCK in mediating aspects of these behaviours has been studied in a variety of behavioural paradigms, but inconsistent results have led to confusion regarding the precise role of the receptor subtypes in mediating behaviour.

Cholecystokinin modulation of mesolimbic dopamine function: regulation of motivated behaviour.

This article reviews evidence and presents a hypothesis regarding the effects of stress on motivated behaviour, and in particular the observation that stress can have both motivationally inhibitory and motivationally facilitatory effects. This issue will be addressed with regard to psychostimulant self-administration, and the role that the neurobiological mechanisms underlying motivated behaviour are thought to be involved in the evolution of addictions. Evidence from animal studies shows that stress and stress-related hormones such as corticosterone can facilitate mesolimbic dopamine function and the behavioural effects of psychostimulants, particularly at lower levels of stress.

Decreased CCK(B) receptor binding in rat amygdala in animals demonstrating greater anxiety-like behavior.

Rationale: The potentiation of the acoustic startle response (ASR) by stimuli associated with aversive events is mediated via the amygdala and is used as an index of "anxiety" and "fear". In laboratory animals, cholecystokinin(B) (CCK(B)) agonists increase anxiety and fear and activation of amygdala CCK(B) receptors potentiates ASR. Additionally, antagonism of CCK(B) receptors attenuates fear-potentiated ASR.

Low-dose dexamethasone challenge in women with atypical major depression: pilot study.

Objective: To examine if atypical depression may be associated with hypersuppression of the hypothalamic-pituitary-adrenal (HPA) axis.

Method: Eight women with atypical major depression and 11 controls with no history of psychiatric illness, matched on age and body mass index, were challenged with low-dose dexamethasone (0.25 mg and 0.