Ventral Midbrain NTS1 Receptors Mediate Conditioned Reward Induced by the Neurotensin Analog, D-Tyr[11]neurotensin.

The present study was aimed at characterizing the mechanisms by which neurotensin (NT) is acting within the ventral midbrain to induce a psychostimulant-like effect. In a first experiment, we determine which subtype(s) of NT receptors is/are involved in the reward-inducing effect of ventral midbrain microinjection of NT using the conditioned place-preference (CPP) paradigm. In a second study, we used in vitro patch clamp recording technique to characterize the NT receptor subtype(s) involved in the modulation of glutamatergic neurotransmission (excitatory post-synaptic current, EPSC) in ventral tegmental neurons that expressed ([Formula: see text]), or do not express ([Formula: see text]), a hyperpolarization-activated cationic current.

CRF2 Receptor Deficiency Eliminates the Long-Lasting Vulnerability of Motivational States Induced by Opiate Withdrawal.

Vulnerability to stressful life events is a hallmark of drug dependence that may persist long after cessation of drug intake and dramatically fuel key clinical features, such as deregulated up-shifted motivational states and craving. However, to date, no effective therapy is available for reducing vulnerability to stressful events in former drug users and drug-dependent patients, mostly because of poor knowledge of the mechanisms underlying it. In this study, we report that genetic inactivation of the stress-responsive corticotropin-releasing factor receptor-2 (CRF2-/-) completely eliminates the reemergence of increased nonrewarded nose-pokes, reflecting up-shifted motivational states, triggered by ethological environmental stressors long after cessation of morphine administration in mice.

Role of context in neurotensin-induced sensitization to the locomotor stimulant effect of amphetamine.

Previous studies have shown that repeated central injections of neurotensin, or its active analog, D-Tyr([11])neurotensin, sensitize to the locomotor stimulant effect of amphetamine. The development of sensitization to amphetamine can be modulated by contextual stimuli associated with the drug and as a consequence the expression of sensitization becomes context-dependent. The present study was thus aimed at determining whether the induction of amphetamine sensitization by neurotensin is modulated by the context in which neurotensin is administered.

The corticotropin-releasing factor receptor-2 mediates the motivational effect of opiate withdrawal.

Altered motivational processes are key features of drug dependence and withdrawal, yet their neural mechanisms remain largely unknown. The present study shows that genetic disruption of the corticotropin-releasing factor receptor-2 (CRF₂-/-) does not impair motivation for palatable food in drug-naïve mice. However, CRF₂ receptor-deficiency effectively reduces the increase in palatable food-driven motivation induced by opiate withdrawal.

Increased motivation to eat in opiate-withdrawn mice.

Rationale: In drug-dependent individuals, the primary excessive motivation is for drugs. Studies also indicate altered interest for "natural" rewarding activities associated with motivational disorders that may be relevant to drug dependence. However, to date, the impact of drug dependence and withdrawal upon motivation for "natural" rewards remains unclear.