Dysfunction of parvalbumin (PV)-positive GABAergic interneurons (PVIs) within the prefrontal cortex (PFC) has been implicated in schizophrenia pathology. It is however unclear, how impaired signaling of these neurons may contribute to PFC dysfunction. To identify how PVIs contribute to PFC-dependent behaviors we inactivated PVIs in the PFC in mice using region- and cell-type-selective expression of tetanus toxin light chain (TeLC) and compared the functional consequences of this manipulation with non-cell-type-selective perturbations of the same circuitry. By sampling for behavioral alterations that map onto distinct symptom categories in schizophrenia, we show that dysfunction of PVI signaling in the PFC specifically produces deficits in the cognitive domain, but does not give rise to PFC-dependent correlates of negative or positive symptoms. Our results suggest that distinct aspects of the complex symptomatology of PFC dysfunction in schizophrenia can be attributed to specific prefrontal circuit elements.

Background and purpose:  Obesity is a severe health problem in the modernized world and understanding the central nervous mechanisms underlying food‐seeking behaviour and reward are at the forefront of medical research. Cannabinoid receptors have proven an efficient target to suppress hunger and weight gain by their pharmacological inactivation.Experimental approach:  A standard fasted protocol and a novel long‐term home‐cage observation system with free‐feeding animals were used to assess the feeding behaviour of mice treated with the CB₁ antagonist AM251. Similarly, the effects of the phytocannabinoid Δ⁹‐tetrahydrocannabivarin (Δ⁹‐THCV), which behaves like a CB₁ antagonist, were also determined in free‐feeding animals.Key results:  AM251 suppressed food intake and weight gain in fasted and non‐fasted animals. The suppression of food intake by AM251 (10 mg·kg⁻¹) endured for a period of 6–8 h when administered acutely, and was continuous when injected for four consecutive days. Pure Δ⁹‐THCV also induced hypophagia and weight reduction at doses as low as 3 mg·kg⁻¹. No rebound was observed on the following day with all drug groups returning to normal activity and feeding regimes. However, a Δ⁹‐THCV‐rich cannabis‐extract failed to suppress food intake and weight gain, possibly due to residual Δ⁹‐tetrahydrocannabinol (Δ⁹‐THC) in the extract. This Δ⁹‐THC effect was overcome by the co‐administration of cannabidiol.Conclusions and implications:  The data strongly suggest (i) the long‐term home‐cage observation system is a sensitive and obesity‐relevant tool, and (ii) the phytocannabinoid Δ⁹‐THCV is a novel compound with hypophagic properties and a potential treatment for obesity.